Niklas Mattsson-Carlgren

• MD, PhD
• Professor (Associate) at Lund University

Purpose Among visually Tau-PET-positive scans, large variation exists in the size of the visually tau-positive area. Here, we propose a metric quantifying the spatial extent of visual Tau-PET-positivity, termed “TAU-SPEX”, and evaluate associations with visual read status, neurofibrillary tangle (NFT) pathology at autopsy, and cognition. Methods [...

Aging and Alzheimer's disease (AD) are associated with alterations in functional connectivity (FC), yet their spatial and temporal characteristics remain debated. Whole-cortex functional gradients, which organize regions along axes of functional similarity, are positioned here as a framework for understanding such alterations. Across two independen...

Importance While clinical disease stages remained largely unchanged in the 2024 update of the Alzheimer disease (AD) criteria, tau–positron emission tomography (PET) was introduced as a core biomarker and its spatial extent was incorporated into the revised biological stages of the disease. It is important to consider both the clinical and the biol...

INTRODUCTION We evaluated differences in p‐tau levels between Alzheimer's disease (AD), a condition with brain‐specific changes in p‐tau, and amyotrophic lateral sclerosis (ALS), a condition associated with increases in peripheral p‐tau levels. METHODS Cerebrospinal fluid and plasma from 668 participants were analyzed using immunoassays specific f...

In Alzheimer's disease (AD), tau pathology accumulates gradually throughout the brain, with clinical decline reflecting tau progression. A comprehensive understanding of, first, whether tau propagation is predominantly governed by connectome-based diffusion, regional vulnerability, or an interplay of both, and second, which types of brain connectiv...

The distribution of tau pathology in Alzheimer’s disease (AD) shows remarkable inter-individual heterogeneity, including hemispheric asymmetry. However, the factors driving this asymmetry remain poorly understood. We explored whether tau asymmetry is linked to i) reduced inter-hemispheric brain connectivity (potentially restricting tau spread), or...

Plasma biomarkers are emerging as noninvasive tools to detect neurodegenerative diseases and monitor treatments in clinical trials. The bPRIDE study investigates blood-based biomarkers to improve the differential diagnosis and molecular staging of Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Using pr...

Global implementation of blood tests for Alzheimer’s disease (AD) would be facilitated by easily scalable, cost-effective and accurate tests. In the present study, we evaluated plasma phospho-tau217 (p-tau217) using predefined biomarker cutoffs. The study included 1,767 participants with cognitive symptoms from 4 independent secondary care cohorts...

Insoluble tau aggregates within neurofibrillary tangles are a defining neuropathological feature of Alzheimer’s disease (AD) and closely correlate with clinical symptoms. Although tau pathology can be assessed using tau positron emission tomography, a more accessible biomarker is needed for diagnosis, prognosis and tracking treatment effects. Here...

Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer’s disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts and 1,474 individuals, we show that plasma...

Background: Plasma p-tau217 and tau PET are biomarkers reflecting partly different aspects of Alzheimer's disease pathology. Plasma p-tau217 may become abnormal earlier in the disease process, potentially capturing the initial alterations of tau metabolism, whereas tau PET provides spatially detailed information about aggregated tau that could more...

INTRODUCTION Tau positron emission tomography (PET) is a reliable neuroimaging technique for assessing regional load of tau pathology in the brain, but its routine clinical use is limited by cost and accessibility barriers. METHODS We thoroughly investigated the ability of various machine learning models to predict clinically useful tau‐PET compos...

The Aβ42/Aβ40 ratio in the cerebrospinal fluid (CSF) and the concentrations of neurofilament light (NfL) and total tau (t-tau) are changed in the early stages of Alzheimer’s disease (AD)¹, but their neurobiological correlates are not entirely understood. Here, we used 5xFAD transgenic mice to investigate the associations between these CSF biomarker...

DOPA Decarboxylase (DDC) has been proposed as a cerebrospinal fluid (CSF) biomarker with increased concentrations in Lewy body disorders (LBDs) and highest levels in patients receiving dopaminergic treatment. Here we evaluate plasma DDC, measured by proximity extension assay, and the effect of dopaminergic treatment in three independent LBD (with a...

The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). While APOE4 is strongly associated with amyloid-beta (Aβ), its relationship with tau accumulation is less understood. Studies evaluating the role of APOE4 on tau accumulation showed conflicting results, particularly regarding the independence of these assoc...

Background Tau‐PET imaging allows in‐vivo detection of neurofibrillary tangles. One tau‐PET tracer (i.e., [18F]flortaucipir) has received FDA‐approval for clinical use, and multiple other tau‐PET tracers have been implemented into clinical trials for participant selection and/or as a primary or secondary outcome measure. To optimize future use of t...

Background Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer’s disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. Method To unco...

Background female sex has been associated with faster tau accumulation over time and greater resilience in Alzheimer’s disease. However, relatively few studies have examined regional tau accumulation rates and cognitive resilience in a large amyloid‐positive cohort. Method We included n=761 amyloid‐positive (A+) participants from the Swedish BioFI...

Background With the development of disease modifying therapies targeting specific pathologies, accurate in vivo biomarkers have become increasingly important for disease classification. Recently, tests for neuronal a‐synuclein (Lewy body) pathology have become available, complementing pre‐existing tests for Alzheimer’s disease (AD) pathology (Aß an...

Background Tau pathology, a hallmark of Alzheimer’s disease (AD), is thought to spread cell‐to‐cell via axonal connections, beginning focally before expanding throughout the brain. This study uses computational models to investigate the interplay between network spread and regional vulnerability in influencing tau spread, focusing specifically on M...

Background Plasma phosphorylated tau (p‐tau), particularly p‐tau217, has demonstrated its reliability as a biomarker for diagnosing Alzheimer's disease (AD). Coming challenges in the field include determining whether quantifying additional plasma phosphorylated, and non‐phosphorylated tau species could enhance diagnostic accuracy, prognosis, and im...

Background An accurate blood test for Alzheimer’s disease (AD) could streamline the diagnostic work‐up and treatment of AD. Our aim was to evaluate an AD blood test in primary and secondary care, using predefined biomarker cutoffs and prospective analyses of plasma samples. Method 940 prospective and unselected patients seeking medical evaluation...

Background An accurate prediction of Alzheimer’s disease (AD) progression is important for patient management and optimization of participant selection for trials. Here, we compared and combined plasma p‐tau217 and tau‐PET measures for predicting longitudinal cognitive decline and clinical progression in cognitively unimpaired participants. Method...

Background With the development of disease modifying therapies targeting specific pathologies, accurate in vivo biomarkers have become increasingly important for disease classification. Recently, tests for neuronal α‐synuclein (Lewy body) pathology have become available, complementing pre‐existing tests for Alzheimer’s disease (AD) pathology (Aβ an...

Background female sex has been associated with faster tau accumulation over time and greater resilience in Alzheimer’s disease. However, relatively few studies have examined regional tau accumulation rates and cognitive resilience in a large amyloid‐positive cohort. Method We included n=761 amyloid‐positive (A+) participants from the Swedish BioFI...

Background Identification of concomitant Lewy Body (LB) pathology might be important for the diagnostic and prognostic work‐up of Alzheimer’s disease (AD) in clinical practice and trials. Here, we aimed to determine whether the presence of LB pathology exacerbates AD‐related disease progression. Methods Cognitively impaired (Mild Cognitive Impairm...

Background Several studies have recently emerged describing relationships between cerebrospinal fluid (CSF) proteins and beta‐amyloid (Aβ) and tau pathology. While these studies have primarily characterized Alzheimer’s disease (AD) proteinopathies using CSF markers, positron emission tomography (PET) more accurately captures these pathologies, espe...

Background Phase 3 trials of successful anti‐amyloid therapies in Alzheimer's disease (AD) have indicated better clinical efficacy in people with less severe disease. Plasma biomarkers will be essential for efficient screening of participants in future primary prevention clinical trials testing anti‐amyloid therapies in cognitively unimpaired (CU)...

Background Fluid biomarkers represent an informative and cost‐effective way to detect and monitor Alzheimer’s disease (AD). However, as we recently showed, the overall proteome average in CSF exhibits a non‐disease related average signal (inter‐individual variability), which can reduce the precision of concentration based CSF AD biomarkers.¹ Now, w...

Background A generative model of tau PET was applied to multiple cohorts across the Alzheimer's disease (AD) spectrum, revealing longitudinal changes in tau production and transport. A generalisation of the model accounts for amyloid, tau and neurodegeneration (ATN) interactions and accurately explains longitudinal ATN biomarker data, adding potent...

Background Recent results from clinical trials in Alzheimer’s disease (AD) emphasize the importance of treating early‐stage disease. However, recruitment of preclinical AD participants is difficult due to the lack of symptoms, and the costs and/or invasiveness of established CSF and PET tests. We aimed to investigate whether plasma p‐tau217 could b...

Background Alpha‐synuclein pathology underlies Lewy body diseases and can also occur comorbid to other neurodegenerative pathologies. The lack of an in vivo measure for alpha‐synuclein pathology until recently has limited thorough characterization of its brain atrophy pattern, especially during early disease stages. We therefore aimed to assess the...

Background We assessed the efficacy of four plasma phospho‐tau217 (p‐tau217) biomarkers in a head‐to‐head comparison, and against two clinically available CSF biomarkers for Alzheimer’s disease (AD). Method Samples were analyzed from 1009 individuals from the Swedish BioFINDER‐2 cohort (Table 1). We included the following biomarkers: %p‐tau217Wash...

Background Blood‐based biomarkers have demonstrated great promise for identifying biomarker‐confirmed Alzheimer's disease. We aimed to evaluate whether blood‐based biomarkers could optimize the referral of memory clinic patients to a tau‐PET exam, which is crucial for prognostic evaluation. Method The study measured various plasma biomarkers (Aβ42...

Background Tau‐PET imaging allows in‐vivo detection of neurofibrillary tangles. One tau‐PET tracer (i.e., [¹⁸F]flortaucipir) has received FDA‐approval for clinical use, and multiple other tau‐PET tracers have been implemented into clinical trials for participant selection and/or as a primary or secondary outcome measure. To optimize future use of t...

Background With the emergence of Alzheimer's disease (AD) disease‐modifying therapies, identifying patients who could benefit from these treatments becomes critical. We evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid‐β (Aβ) plaques and tau tangles. Method Plasma %p‐ta...

Background A key characteristic of Alzheimer’s disease (AD) is cerebral aggregation of tau. These aggregates can be quantified and localized with positron emission tomography (PET), which improves the diagnostic and prognostic work‐up of AD. However, tau‐PET is expensive and not available in clinical settings globally. With emerging disease‐modifyi...

Background Cerebrospinal fluid (CSF) proteomics allows for characterization of multiple disease‐related biological processes in vivo . These processes likely occur along temporal cascades mirroring disease evolution. This study describes interindividual variation in these cascades, in the context of Alzheimer’s disease. Method Participants were re...

Background Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer’s disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. Method To unco...

Background The success of selecting high risk or early-stage Alzheimer’s disease individuals for the delivery of clinical trials depends on the design and the appropriate recruitment of participants. Polygenic risk scores (PRS) show potential for identifying individuals at risk for Alzheimer’s disease (AD). Our study comprehensively examines AD PRS...

Evidence from neuropathological cohorts indicates that a CSF α-synuclein (α-syn) seed amplification assay (SAA) may provide quantitative kinetic parameters correlating with α-syn pathology burden in patients with Lewy body disease (LBD). Studies are needed to assess their longitudinal trend during the pre-symptomatic and clinical disease phases and...

Disease-specific fluid biomarkers are in demand for parkinsonian syndromes. Corticotropin-releasing hormone was proposed as a biomarker for Lewy body disease. As such, this project aimed to confirm corticotropin-releasing hormone as a potential biomarker for different parkinsonian syndromes. Corticotropin-releasing hormone and misfolded α-synuclein...

Recently approved anti-amyloid immunotherapies for Alzheimer’s disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the...

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer’s disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET,...

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder characterized by brain aggregation of β-amyloid (Aβ) peptides and phosphorylated tau (P-tau) proteins. Extracellular vesicles (EVs) can be isolated and studied for potential roles in disease. While several studies have tested plasma-derived EVs in AD, few have analyzed EVs from c...

Background In Alzheimer’s disease (AD), the associations between tau pathology and brain atrophy and cognitive decline are well established, but imperfect. We investigate whether cerebrospinal fluid (CSF) biomarkers of biological processes (vascular, synaptic, and axonal integrity, neuroinflammation, neurotrophic factors) explain the disconnection...

The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer""s disease (AD). While APOE4 is strongly associated with amyloid-beta (Aβ) accumulation, its relationship with tau accumulation is less understood. Studies evaluating the role of APOE4 on tau accumulation have shown conflicting results, particularly regarding the independe...

Background The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer’s disease (EOAD). Yet, detailed examination of MTL subfields and drivers of atrophy in amnestic EOAD is lacking. Methods BioFINDER-2 participants with memory impairment, abnormal amyloid-β and tau-PET were included. Forty-one amnestic EOAD in...

Identifying concomitant Lewy body (LB) pathology through seed amplification assays (SAA) might enhance the diagnostic and prognostic work-up of Alzheimer’s disease (AD) in clinical practice and trials. This study examined whether LB pathology exacerbates AD-related disease progression in 795 cognitively impaired individuals (Mild Cognitive Impairme...

INTRODUCTION We examined the relations of misfolded alpha synuclein (α‐synuclein) with Alzheimer's disease (AD) biomarkers in two large independent cohorts. METHODS We included Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably Two (BioFINDER‐2) and Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (n = 2315, c...

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by the aggregation of β-amyloid (Aβ) and tau in the brain. Breakthroughs in disease-modifying treatments targeting Aβ bring new hope for the management of AD. But to effectively modify and someday even prevent AD, a better understanding is needed of the biolo...

Proteomics can shed light on the dynamic and multifaceted alterations in neurodegenerative disorders like Alzheimer’s disease (AD). Combining radioligands measuring β-amyloid (Aβ) plaques and tau tangles with cerebrospinal fluid proteomics, we uncover molecular events mirroring different stages of AD pathology in living humans. We found 127 differe...

Importance The lack of an in vivo measure for α-synuclein (α-syn) pathology until recently has limited thorough characterization of its brain atrophy pattern, especially during early disease stages. Objective To assess the association of state-of-the-art cerebrospinal fluid (CSF) seed amplification assays (SAA) α-syn positivity (SAA α-syn+) with m...

Importance An accurate blood test for Alzheimer disease (AD) could streamline the diagnostic workup and treatment of AD. Objective To prospectively evaluate a clinically available AD blood test in primary care and secondary care using predefined biomarker cutoff values. Design, Setting, and Participants There were 1213 patients undergoing clinica...

Importance Phase 3 trials of successful antiamyloid therapies in Alzheimer disease (AD) have demonstrated improved clinical efficacy in people with less severe disease. Plasma biomarkers will be essential for efficient screening of participants in future primary prevention clinical trials testing antiamyloid therapies in cognitively unimpaired (CU)...

Tau aggregation measured with PET and neurodegeneration measured with MRI are closely associated with cognitive decline in Alzheimer's disease, but the independent contributions of baseline and longitudinal measures of these imaging markers to cognitive decline remain unclear. Here, we tested a) independent associations between baseline and rate of...

This scientific commentary refers to ‘Towards cascading genetic risk in Alzheimer’s disease’ by Altmann et al. (https://doi.org/10.1093/brain/awae176).

Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder where pathophysiological changes begin decades before the onset of clinical symptoms. Analysis of brain atrophy patterns using structural MRI and multivariate data analysis are an effective tool in identifying patients with subjective cognitive decline (SCD) at higher r...

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarkers for reliable detection of Alzheimer′s disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared leading plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau...

Plasma p-tau217 and Tau-PET are strong prognostic biomarkers in Alzheimer’s disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In this head-to-head comparison study including 9 cohorts and 1534 individuals, we found that plasma p-tau217 and medial temporal lo...

Importance An accurate prognosis is especially pertinent in mild cognitive impairment (MCI), when individuals experience considerable uncertainty about future progression. Objective To evaluate the prognostic value of tau positron emission tomography (PET) to predict clinical progression from MCI to dementia. Design, Setting, and Participants Thi...

The pathophysiology underlying various manifestations of cerebral small vessel disease (cSVD) remains obscure. Using cerebrospinal fluid proximity extension assays and co-expression network analysis of 2,943 proteins, we found common and distinct proteomic signatures between white matter lesions (WML), microbleeds and infarcts measured in 856 livin...

Tau positron emission tomography (PET) is a reliable neuroimaging technique for assessing regional load of tau pathology in the brain, commonly used in Alzheimer’s disease (AD) research and clinical trials. However, its routine clinical use is limited by cost and accessibility barriers. Here we explore using machine learning (ML) models to predict...

Background The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer’s disease (EOAD). Yet, detailed examination of MTL subfield volumes and drivers of atrophy in amnestic EOAD is lacking. Methods BioFINDER-2 participants with memory impairment, abnormal amyloid-β status and tau-PET were included. Forty-one EO...

Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer’s disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-...

Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer’s disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrop...

Background The purpose was to evaluate glial fibrillary acidic protein (GFAP) and total-tau in plasma as predictors of poor neurological outcome after out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA), including comparisons with neurofilament light (NFL) and neuron-specific enolase (NSE). Methods Retrospective multicentre observational...

Background Predicting future Alzheimer’s disease (AD)-related cognitive decline among individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) is an important task for healthcare. Structural brain imaging as measured by magnetic resonance imaging (MRI) could potentially contribute when making such predictions. It is un...

Blood-based biomarkers for screening may guide tau positrion emissition tomography (PET) scan referrals to optimize prognostic evaluation in Alzheimer’s disease. Plasma Aβ42/Aβ40, pTau181, pTau217, pTau231, NfL, and GFAP were measured along with tau-PET in memory clinic patients with subjective cognitive decline, mild cognitive impairment or dement...

With the emergence of Alzheimer’s disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. In this study, we evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217...

Background Novel phosphorylated-tau (p-tau) blood biomarkers (e.g., p-tau181, p-tau217 or p-tau231), are highly specific for Alzheimer’s disease (AD), and can track amyloid-β (Aβ) and tau pathology. However, because these biomarkers are strongly associated with the emergence of Aβ pathology, it is difficult to determine the contribution of insolubl...

Background Antibody-based immunoassays have enabled quantification of very low concentrations of phosphorylated tau (p-tau) protein forms in cerebrospinal fluid (CSF), aiding in the diagnosis of AD. Mass spectrometry enables absolute quantification of multiple p-tau variants within a single run. The goal of this study was to compare the performance...

Background Recently, we demonstrated the sensitivity of a novel CSF mass spectrometer‐based assay, which enabled the assessment of multiple phospho‐tau (pTau) forms (pT181, pS199, pS202, pT205, pT217, pT231, and pS396) and two non‐phosphorylated peptides. Initial results suggested that there may be disease associated differences across pTau species...

Background In the ATN ( A myloid b, T au, N eurodegeneration) biomarker research framework proposed for Alzheimer’s Disease (AD), a critical need is the identification of robust markers of neurodegeneration (“N”) for more accurate disease state diagnosis and prognosis. Targeted proteomic profiling can be highly valuable for identifying such markers...

Background Cerebral small vessel disease (SVD) is a cerebrovascular condition associated with age that contributes to dementia, stroke, and other neurological disorders. White matter lesions (WML), microbleeds, and infarcts are hallmarks of SVD, but their molecular mechanisms are poorly understood. The aim of this study was to investigate the CSF p...

Background Plasma‐based biomarkers able to depict the molecular diversity associated to Alzheimer´s disease (AD) are needed to better track disease progression and for developing biological therapies targeting different pathomechanisms. Here we aimed to identify plasma protein changes covering different biological pathways along the AD continuum an...

Fluid biomarkers of amyloid and tau, including measures in both cerebrospinal fluid and plasma, have been used extensively in clinical and translational studies of Alzheimer’s disease and other neurodegenerative diseases. These biomarkers are now also increasingly used in clinical practice to inform on diagnosis and prognosis. Despite a successful...

Background CSF biomarkers are key AD descriptors, but the CSF volume as well as the production and clearance rates of proteins varies in individuals. Adjusting for reference proteins, which reflect these factors, might improve the accuracy of CSF biomarkers, similar to when normalizing CSF Aβ42 levels to Aβ40 levels. For other biomarkers, individua...

Background The latest generation of plasma biomarkers (phosphorylated Tau181 (pTau181), Glial fibrillary acidic protein (GFAP), Neurofilament light (NFL) and the Amyloid‐beta ratio (Aβ42/40) have demonstrated high accuracy to detect AD pathology in either CSF/PET by many single‐center studies. Here we assess which markers (alone/combined) can best...

Background The introduction of the A/T/(N) (β‐amyloid/tau/neurodegeneration) framework has revealed an A‐T+ (β‐amyloid‐negative/tau‐positive) group which has been named suspected non‐Alzheimer’s pathophysiology. Cerebrospinal fluid (CSF) markers are often utilized to divide individuals in the A and T categories, but it is unclear what elevated CSF...

Background Recent studies suggest that microtubule‐binding region (MTBR) tau fragments may be markers of tau tangles in Alzheimer’s disease (AD) when used in ratio with total tau (MTBR‐tau/T‐tau) to normalize for T‐tau secretion. One such candidate marker is MTBR‐tau containing residue 368 (MTBR‐tau368). In this study, it was cross‐sectionally eval...

Background An important end‐point for disease‐modifying treatments is to target the accumulation of tau. This highlights the need to determine which individuals are most likely to accumulate tau in the future. Different biomarkers of tau become abnormal at different stages of Alzheimer’s disease and capturing the evolution of tau pathology in its e...

Background In contrast to amyloid‐PET and MRI, tau‐PET imaging has not been integrated into clinical practice even though it shows a close relationship with clinical symptoms. With the present study, we aim to assess the performance of tau‐PET to predict conversion to dementia (all‐cause and AD) in individuals with mild cognitive impairment (MCI),...

Background Tau pathology is strongly associated with clinical symptoms, possibly (partly) through the manifestation of neurodegeneration. However, independent pathways between tau pathology and clinical symptoms have been suggested. Longitudinal studies investigating the role of tau vs neurodegeneration on cognitive and behavioral changes across th...

Background Tau pathology is strongly associated with clinical symptoms, possibly (partly) through the manifestation of neurodegeneration. However, independent pathways between tau pathology and clinical symptoms have been suggested. Longitudinal studies investigating the role of tau vs neurodegeneration on cognitive and behavioral changes across th...

Background In contrast to amyloid‐PET and MRI, tau‐PET imaging has not been integrated into clinical practice even though it shows a close relationship with clinical symptoms. With the present study, we aim to assess the performance of tau‐PET to predict conversion to dementia (all‐cause and AD) in individuals with mild cognitive impairment (MCI),...

Importance Antiamyloid immunotherapies against Alzheimer disease (AD) are emerging. Scalable, cost-effective tools will be needed to identify amyloid β (Aβ)–positive patients without an advanced stage of tau pathology who are most likely to benefit from these therapies. Blood-based biomarkers might reduce the need to use cerebrospinal fluid (CSF) o...

Background: Predicting future Alzheimer’s disease (AD)-related cognitive decline among individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) is an important task for healthcare. Structural brain imaging as measured by magnetic resonance imaging (MRI) could potentially contribute when making such predictions. It is u...

Aggregation of the hyperphosphorylated tau protein is a central driver of Alzheimer’s disease, and its accumulation exhibits a rich spatio-temporal pattern that unfolds during the course of the disease, sequentially progressing through the brain across axonal connections. It is unclear how this spatio-temporal process is orchestrated – namely, to w...

Background Impaired gait can precede dementia. The associations between gait parameters and brain pathologies are therefore of interest. Objective To explore how different brain pathologies (i.e., vascular and Alzheimer’s) are associated with specific gait parameters from various gait components in persons with mild cognitive impairment (MCI), who...

The diagnosis of Parkinsonian disorders is currently based on clinical criteria, which have limited sensitivity until most dopaminergic neurons are lost. Here we show that cerebrospinal fluid levels of DOPA decarboxylase (DDC) (also known as aromatic l-amino acid decarboxylase) can accurately identify patients with Lewy body disease (LBD) (area und...

Background Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder without a cure. Innovative disease models, such as induced neurons (iNs), could enhance our understanding of AD mechanisms and accelerate treatment development. However, a review of AD human iN studies is necessary to consolidate knowledge. Objective The objective of thi...

Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis,...