Andrew J Saykin

• PsyD
• Professor at Indiana University School of Medicine - Lafayette

Importance Understanding the characteristics of discordance between plasma biomarkers and positron emission tomography (PET) results in Alzheimer disease (AD) is crucial for accurate interpretation of the findings. Objective To compare (1) medical comorbidities affecting plasma biomarker concentrations, (2) imaging and clinical features, and (3) c...

Intracranial cardiac impulse propagation along penetrating arterioles is vital for both nutrient supply via blood circulation and waste clearance via CSF circulation. However, current neuroimaging methods are limited to simultaneously detecting impulse propagation at pial arteries, arterioles, and between them. We hypothesized that this propagation...

Background: Genome-wide association studies (GWAS) have identified over 1,000 blood pressure (BP) loci and over 80 loci for Alzheimer's disease (AD). Considering BP is an AD risk factor, identifying pleiotropy in BP and cognitive performance measures may indicate mechanistic links between BP and AD. Methods: Genome-wide scans for pleiotropy in BP v...

INTRODUCTION The molecular mechanisms underlying early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) remain incompletely understood, particularly in Asian populations. METHODS RNA‐sequencing was carried out on blood samples from 248 participants in the Seoul National University Bundang Hospital cohort to perform differ...

Brain network dynamics have been extensively explored in patients with subjective cognitive decline (SCD). However, these studies are susceptible to individual differences, scanning parameters, and other confounding factors. Therefore, how to reveal subtle SCD-related subtle changes remains unclear. Cross-sectional and longitudinal resting-state fu...

Alzheimer’s disease (AD) is a debilitating neurodegenerative disease that is marked by profound neurovascular dysfunction and significant cell-specific alterations in the brain vasculature. Recent advances in high throughput single-cell transcriptomics technology have enabled the study of the human brain vasculature at an unprecedented depth. Addit...

INTRODUCTION The exponential growth of genomic datasets necessitates advanced analytical tools to effectively identify genetic loci from large‐scale high throughput sequencing data. This study presents Deep‐Block, a multi‐stage deep learning framework that incorporates biological knowledge into its AI architecture to identify genetic regions as sig...

Background Identification of genetic alleles associated with both Alzheimer’s disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings ar...

Background Despite recognition of the need to increase underrepresented groups (URG) engagement in Alzheimer’s disease and related dementias (ADRD) studies, enrollment remains low. As a first step in examining these disparities, these analyses aimed to compare referral sources for Alzheimer’s Disease Research Centers (ADRC) enrollment of URG partic...

Background Video interfacing is increasingly being used in research and health care. The ‘VCog’ Study seeks to determine whether remote research cognitive assessments are reliable and valid by directly comparing results from in‐person administration of a standardized cognitive battery to the same battery administered remotely by video. The study al...

Background Alzheimer’s disease (AD) is characterized by longitudinal changes of biomarker endophenotypes over the course of the disease prodrome, onset, and progression. The genetic pathways that influence these heterogenous changes in longitudinal endophenotype trajectories may provide insight into disease mechanisms and represent potential therap...

Background Analyzing disease‐linked genetic variants via expression quantitative trait loci (eQTLs) is crucial for identifying disease‐causing genes. Previous research prioritized genes by integrating Genome‐Wide Association Study (GWAS) results with tissue‐level eQTLs. Recent studies explored brain cell type‐specific eQTLs, but they lack a systema...

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 Previous models of resilience to Alzheimer’s Disease (AD) have relied on cross‐sectional designs and inclusion of measures of neuropathology. Here, we present a novel modeling approach incorporating longitudinal data and the use of APOE and higher order interaction terms to approximate neuropathological resilience, vastly increasing part...

Background Recent research emphasizes the significance of white matter tracts and the free‐water (FW) component in understanding cognitive decline. The goal of this study is to conduct a large‐scale assessment on the role of white matter microstructure on longitudinal cognitive decline. Method This study used a cohort collated from seven longitudi...

Background Changes in brain network organization are influenced by aging. Accumulation of amyloid‐beta (Aß) and neurodegeneration in the neocortex are also expected to alter neuronal networks. Therefore, we examined the relationship between aging and brain functional connectivity (FC), as well as the effect of brain Aß on this relationship. Method...

Background Dementia is age‐related with a significant genetic contribution, yet genome‐wide association studies have not fully accounted for heritability. This discrepancy may in part be due to reliance on SNPs and small indels. Whole‐genome sequencing (WGS) data in the Japanese population may reveal population‐specific susceptibility loci for deme...

Background Persons with Alzheimer’s disease and related dementias (ADRD) have been disproportionally impacted by the COVID‐19 pandemic, showing a significantly increased risk of infection and severe illness, including neurocognitive consequences. The National Alzheimer’s Coordinating Center collects rich longitudinal, standardized neurocognitive da...

Background The amyloid‐tau‐neurodegeneration (ATN) framework provides a valuable model for comprehending the pathophysiology and progression of Alzheimer’s disease (AD). However the relationship between and genetic interaction with these three characteristics are complex and not fully understood. Here, we use neuroimaging‐derived quantitative trait...

Background Understanding the relationship between cardiovascular burden, amyloid, and cognition in Alzheimer’s disease (AD) is essential for targeted interventions, especially in ethnically diverse populations where research remains limited. This study aimed to investigate these relationships in a cohort of Korean older adults along the AD spectrum...

Background Adverse social exposome (indexed by high national Area Deprivation Index [ADI]) is linked to structural inequities and increased risk of clinical dementia diagnosis, yet linkage to ADRD neuropathology remains largely unknown. Early work from single site brain banks suggests a relationship, but assessment in large national cohorts is need...

Background We investigated heterogeneities in clinical progression trajectories among cognitively impaired (CI) older adults who were positive for both beta‐amyloid (Aβ) and neurodegeneration biomarkers of Alzheimer’s disease (AD) using trajectory clustering analysis. We then compared clinical and neuroimaging variables across clusters with differe...

Background Despite evidence that Alzheimer’s disease (AD) is highly heritable, there remains substantial “missing” heritability, likely due in part to the effect of rare variants and to the past reliance on case‐control analysis. Here, we leverage powerful endophenotypes of AD (cognitive performance across multiple cognitive domains) in a rare vari...

Background Alzheimer’s disease (AD) patients have decline in cognitive domains including memory, language, visuospatial, and/or executive function and brain pathology including amyloid‐β and tau deposition, neurodegeneration, and frequent vascular co‐pathologies detectable by neuroimaging and/or cerebrospinal fluid biomarkers. However, molecular di...

Background New techniques have been developed to estimate the age when someone converted to amyloid positivity (EAOA) from PET, oftentimes offering information Aβout a participant decades before they joined a research study. EAOA is variable across populations but we do not know the causes for these differences. This study aims to validate APOE ass...

Background Changes in brain network organization are influenced by aging. Accumulation of amyloid‐beta (Aβ) and neurodegeneration in the neocortex are also expected to alter neuronal networks. Therefore, we examined the relationship between aging and brain functional connectivity (FC), as well as the effect of brain Aβ on this relationship. Method...

Background Alzheimer's disease (AD) is a complex neurodegenerative disorder that has impacted millions of people worldwide. Identifying different risk groups converting to AD during the mild cognitive impairment (MCI) stage and determining their genetic basis would be immensely valuable for drug discovery and subsequent clinical treatment. Previous...

Background Cognitive subtypes of Alzheimer’s Dementia (AD), defined by a relative impairment in a particular domain of cognition, have previously been shown to be associated with patterns of gray matter atrophy. Here we assessed the association of these subtypes with patterns of tau deposition measured in vivo using tau PET imaging in the Alzheimer...

Background Greater occupational complexity may be protective against dementia in later life, but it is unclear if it contributes to cognitive resilience and whether different aspects of occupational complexity are associated with resilience. We examined relationships between occupational complexity related to data, people, and things, and cognitive...

Background Understanding the relationship between genetic variations and brain imaging phenotypes is an important issue in Alzheimer's disease (AD) research. As an alternative to GWAS univariate analyses, canonical correlation analysis (CCA) and its deep learning extension (DCCA) are widely used to identify associations between multiple genetic var...

Background Understanding the dynamics of markers throughout Alzheimer’s disease (AD) progression in a representative population is critical for early detection of AD. Most existing studies used a single cohort to model the dynamics of AD‐related markers, which may lead to biased and unreproducible results. The Alzheimer’s Disease Sequencing Project...

Background The eye often reflects changes seen in the brain in neurodegenerative diseases. This study sought to examine the relationship of retinal vasculature measured using optical coherence tomography angiography (OCTA) with temporal lobe neurodegeneration, and cerebral amyloid and tau deposition, in older adults along the Alzheimer’s disease (A...

Background Adverse social exposome (indexed by national Area Deprivation Index [ADI] 80‐100 or ‘high ADI’) is linked to structural inequities and increased risk of Alzheimer’s disease neuropathology. Twenty percent of the US population resides within high ADI areas, predominantly in inner cities, tribal reservations and rural areas. The percentage...

Background The Mediterranean diet has been associated with decreased brain atrophy (Staubo et al. 2016,Alz&Dem), but the MIND (Mediterranean‐Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay) diet, designed for dementia prevention (Morris et al. 2015, Alz&Dem), remains underexplored for its impact on brain atro...

Background Some evidence supports an association between traumatic brain injury (TBI) and greater risk of dementia, but the role of cognitive resilience in this association is poorly understood. Method 2,050 participants from the Framingham Heart Study Offspring cohort who were aged ≥60 year and had a plasma total tau (t‐tau) measure at Exam 8 (20...

Background Shared genetic risk between Alzheimer’s disease (AD) and concussion may help explain the association between concussion and elevated risk for dementia. However, there has been little investigation into whether AD risk genes also associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk sco...

Background Previous studies suggest limited knowledge about Alzheimer’s Disease (AD) is a barrier to underrepresented group participation in AD research. Connections between knowledge of AD and factors like social determinants of health or confidence in biomarker research have not been carefully examined. We hypothesized perceived knowledge about A...

Background Two main risk factors of Alzheimer’s disease (AD) are aging and APOE‐ε4. However, some individuals remain cognitively normal despite having these risk factors. They are considered “cognitively resilient”. This study aimed to identify molecular factors that confer cognitive resilience in APOE‐ε4 carriers ≥ 80 years of age and may serve as...

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 Alzheimer’s disease (AD) pathology occurs in the brain before manifestation of significant cognitive decline. Growing evidence suggests that brain networks such as default mode network (DMN) or salience network, identified through resting‐state functional magnetic resonance imaging (MRI), are affected by AD pathology. In this study, we i...

Background Apathy in patients with Alzheimer’s disease (AD) is associated with significant morbidity. We examined whether interactions between genetic variants related to neurotransmitter systems and regional brain atrophy are associated with apathy in patients with mild cognitive impairment (MCI) and AD. Method For 1162 participants in the Alzhei...

Background Brain network studies in Alzheimer’s disease (AD) have primarily focused on structural and functional connectomes as separate entities. However, it remains unclear how brain structure interacts with brain function in AD. Method We included 75 cognitively unimpaired participants and 49 patients with AD. For each participant, we integrate...

Background There is growing recognition that white matter microstructural integrity is affected in Alzheimer’s disease. The goal of this study was to characterize sex, racial/ethnic, and apolipoprotein (APOE)‐ε4 allele differences in white matter integrity. Methods This study included participants from ADNI, BLSA, ROS/MAP/MARS, and VMAP, all longi...

Background Recent research emphasizes the significance of white matter tracts and the free‐water (FW) component in understanding cognitive decline. The goal of this study is to conduct a large‐scale assessment on the role of white matter microstructure on longitudinal cognitive decline. Method This study used a cohort collated from seven longitudi...

Background: Analyzing disease-linked genetic variants via expression quantitative trait loci (eQTLs) is important for identifying potential disease-causing genes. Previous research prioritized genes by integrating Genome-Wide Association Study (GWAS) results with tissue-level eQTLs. Recent studies have explored brain cell type-specific eQTLs, but t...

Importance The ability to predict the onset of mild cognitive impairment (MCI) and Alzheimer dementia (AD) could allow older adults and clinicians to make informed decisions about dementia care. Objective To assess whether the age at onset of MCI and AD can be predicted using a statistical modeling approach. Design, Setting, and Participants This...

Importance: SuperAgers are oldest-old adults (ages 80+) whose memory performance resembles that of adults in their 50s to mid-60s. Factors underlying their exemplary memory are underexplored in large, racially diverse cohorts. Objective: To determine the frequency of APOE genotypes in non-Hispanic Black and non-Hispanic White SuperAgers compared to...

INTRODUCTION Accurately assessing temporal order of cognitive decline across multiple domains is critical in Alzheimer’s disease (AD). Existing literature presented controversial conclusions likely due to the use of a single cohort and different analytical strategies. METHODS Harmonized composite cognitive measures in memory, language and executiv...

Background Neuropsychiatric symptoms are uncommon at Alzheimer’s Disease (AD) dementia diagnosis but are exhibited by nearly everyone during the course of dementia. Depressive symptoms are common in AD dementia. We sought to determine correlations between memory, executive functioning, language, neuropsychiatric symptoms, and depressive symptoms at...

Background Large‐scale genome‐wide association studies (GWAS) of Alzheimer’s disease (AD) from European ancestry identified many genetic variants associated with clinical diagnosis of AD dementia. However, it remains unclear whether these AD‐related variants are associated with AD biomarkers, particularly hippocampal atrophy, a well‐known neurodege...

Background Despite significant advancements in the development of blood biomarkers for AD, challenges persist due to the complex interplay of genetic and environmental risk factors in AD pathogenesis. Epigenetic processes, including non‐coding RNAs and especially microRNAs (miRs), have emerged as important players in the molecular mechanisms underl...

Background Genome‐wide association studies (GWAS) in Alzheimer’s disease (AD) leveraging endophenotypes beyond case/control diagnosis, such as brain amyloid β pathology, have shown promise in identifying novel variants and understanding their potential functional impact. In this study, we leverage two brain amyloid β pathology measurement modalitie...

Background The Apolipoprotein E ε4 (APOE‐ε4) allele is common in the population, but acts as the strongest genetic risk factor for late‐onset Alzheimer’s disease (AD). Despite the strength of the association, there is notable heterogeneity in the population including a strong modifying effect of genetic ancestry, with the APOE‐ε4 allele showing a s...

Background Non‐coding RNA species, such as microRNA (miRNA), regulate multiple biological and pathological processes by binding to target mRNAs and facilitating alteration of translation levels via complexes such as RNA‐induced silencing complex (RISC). Disrupting this process could contribute to AD pathogenesis by fostering aggregation of hyperpho...

Background Genome‐wide association studies (GWAS) have identified numerous genetic variants associated with Alzheimer’s disease (AD) risk, but genetic variation in the onset and progression of AD pathology is less understood. Accumulation of amyloid‐β (Aβ) in the brain is a key pathological hallmark of AD beginning 10 – 20 years prior to cognitive...

Background There is growing evidence that epigenetic age acceleration may predict late life cognitive decline and dementia, but it is unknown whether this is due to accelerated neurodegeneration or reduction in cognitive resilience. We examined the relationship between epigenetic clocks and domain specific neuropsychological (NP) factor scores, mil...

Background Systemic inflammation plays a pivotal role in many chronic diseases including Alzheimer’s disease (AD). Assessing the composition of immune pathways in neurodegenerative diseases can contribute to precision medicine. Using publicly available transcriptomic data, we sought to elucidate transcriptional networks pertinent to inflammatory pa...

Background “SuperAgers” are older adults (ages 80+) whose cognitive performance resembles that of adults in their 50s to mid‐60s. Factors underlying their exemplary aging are underexplored in large, racially diverse cohorts. Using eight cohorts, we investigated the frequency of APOE genotypes in SuperAgers compared to middle‐aged and older adults....

Background Dementia is age‐related with a significant genetic contribution, yet genome‐wide association studies have not fully accounted for heritability. This discrepancy may in part be due to reliance on SNPs and small indels. Whole‐genome sequencing (WGS) data in the Japanese population may reveal population‐specific susceptibility loci for deme...

Background The relationship between Alzheimer’s disease (AD) pathology and the associated clinical syndrome a patient presents with remains indeterminate. Cognitively‐defined subgroups of AD have revealed distinctions based on relative cognitive impairments, including AD‐Language, where challenges in language are substantial, and AD‐No Domain, wher...

Alzheimer’s disease (AD) is the leading dementia among the elderly with complex origins. Despite extensive investigation into the AD-associated protein-coding genes, the involvement of noncoding RNAs (ncRNAs) and posttranscriptional modification (PTM) in AD pathogenesis remains unclear. Here, we comprehensively characterized the landscape of ncRNAs...

Alzheimer's disease (AD) is a neurodegenerative disorder that results in progressive cognitive decline but without any clinically validated cures so far. Understanding the progression of AD is critical for early detection and risk assessment for AD in aging individuals, thereby enabling initiation of timely intervention and improved chance of succe...

Alzheimer’s disease (AD) is a polygenic disorder with a prolonged prodromal phase, complicating early diagnosis. Recent research indicates that increased astrocyte reactivity is associated with a higher risk of pathogenic tau accumulation, particularly in amyloid-positive individuals. However, few clinical tools are available to predict which indiv...

INTRODUCTION The effects of sex and apolipoprotein E (APOE)—Alzheimer's disease (AD) risk factors—on white matter microstructure are not well characterized. METHODS Diffusion magnetic resonance imaging data from nine well‐established longitudinal cohorts of aging were free water (FW)–corrected and harmonized. This dataset included 4741 participant...

The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to optimize and validate biomarkers for clinical trials while sharing all data and biofluid samples with the global scientific community. ADNI has been instrumental in standardizing and validating amyloid beta (Aβ) and tau positron emission tomography (PET) imaging. ADNI...

Single cell RNA-seq (scRNA-seq) technologies provide unprecedented resolution representing transcriptomics at the level of single cell. One of the biggest challenges in scRNA-seq data analysis is the cell type annotation, which is usually inferred by cell separation approaches. In-silico algorithms that accurately identify individual cell types in...

INTRODUCTION We investigated the hypothesis that tau burden in the locus coeruleus (LC) correlates with tau accumulation in cortical regions according to the Braak stages and examined whether the relationships differed according to cortical amyloid beta (Aβ) deposition. METHODS One hundred and seventy well‐characterized participants from an ongoin...

More than 2 million older Americans from underrepresented racial and ethnic minority groups (URGs) have early‐stage Alzheimer's disease and related dementias (ADRD). There are very few scalable recruitment strategies, particularly for Black older adults, to accelerate participation in ADRD research. The Indiana Alzheimer's Disease Research Center (...

Traumatic brain injury (TBI) has been discussed as a risk factor for Alzheimer's disease (AD) due to its association with AD risk and earlier cognitive symptom onset. However, the mechanisms behind this relationship are unclear. Some studies have suggested TBI may increase pathological protein deposition in an AD-like pattern; others have failed to...

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer’s Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-di...

INTRODUCTION The influence of genetic variation on tau protein aggregation, a key factor in Alzheimer's disease (AD), remains not fully understood. We aimed to identify novel genes associated with brain tau deposition using pathway‐based candidate gene association analysis in a Korean cohort. METHODS We analyzed data for 146 older adults from the...

Background Apathy in patients with Alzheimer's disease (AD) is associated with significant morbidity and is often one of the first neuropsychiatric symptoms to present in mild cognitive impairment (MCI). Apathy is associated with accelerated cognitive decline and atrophy in fronto-striatal regions of the brain. Previous work has shown a link betwee...

Alzheimer’s disease (AD) is a highly heritable brain dementia, along with substantial failure of cognitive function. Large-scale genome-wide association studies (GWASs) have led to a set of SNPs significantly associated with AD and related traits. GWAS hits usually emerge as clusters where a lead SNP with the highest significance is surrounded by o...

Background Alzheimer's disease and related dementias (ADRD) frequently co-occur with comorbidities such as diabetes and cardiovascular diseases in elderly populations. Objective Utilize a life-course approach to identify genetic variants that are associated with the co-occurrence of ADRD and another comorbid condition. Methods Research data from...

INTRODUCTION Despite the recognized importance of including ethnic diversity in Alzheimer's disease (AD) research, substantial knowledge gaps remain, particularly in Asian populations. METHODS RNA sequencing was performed on blood samples from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) to per...

This study was conducted to clarify patterns of cortico-limbic volume abnormalities in late life depression (LLD) relative to non-depressed (ND) adults matched for amyloid β (Aβ) deposition and to evaluate the relationship of volume abnormalities with cognitive performance. Participants included 116 LLD and 226 ND. Classification accuracy of LLD st...

BACKGROUND Limited research has explored the effect of cardiovascular risk and amyloid interplay on cognitive decline in East Asians. METHODS Vascular burden was quantified using Framingham's General Cardiovascular Risk Score (FRS) in 526 Korean Brain Aging Study (KBASE) participants. Cognitive differences in groups stratified by FRS and amyloid p...

INTRODUCTION The genetic pathways that influence longitudinal heterogeneous changes in Alzheimer's disease (AD) may provide insight into disease mechanisms and potential therapeutic targets. METHODS Longitudinal endophenotypes from the Alzheimer's Disease Neuroimaging Initiative (ADNI) representing amyloid, tau, neurodegeneration (A/T/N), and cogn...

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon)...

Genome-wide association studies (GWAS) have identified >80 Alzheimer’s disease and related dementias (ADRD)-associated genetic loci. However, the clinical outcomes used in most previous studies belie the complex nature of underlying neuropathologies. Here we performed GWAS on 11 ADRD-related neuropathology endophenotypes with participants drawn fro...

Alzheimer’s disease (AD) is associated with heterogeneous atrophy patterns. We employed a semi-supervised representation learning technique known as Surreal-GAN, through which we identified two latent dimensional representations of brain atrophy in symptomatic mild cognitive impairment (MCI) and AD patients: the “diffuse-AD” (R1) dimension shows wi...

Tensor Canonical Correlation Analysis (TCCA) is a commonly employed statistical method utilized to examine linear associations between two sets of tensor datasets. However, the existing TCCA models fail to adequately address the heterogeneity present in real-world tensor data, such as brain imaging data collected from diverse groups characterized b...

Background Despite the need to increase engagement of underrepresented groups (URG) in Alzheimer’s disease and related dementias (ADRD) studies, enrollment remains low. Objective Compare referral sources across racial and ethnic groups among participants enrolled in ADRC studies. Methods Data for this cross-sectional secondary analysis were extra...

INTRODUCTION The exponential growth of genomic datasets necessitates advanced analytical tools to effectively identify genetic loci from large-scale high throughput sequencing data. This study presents Deep-Block, a multi-stage deep learning framework that incorporates biological knowledge into its AI architecture to identify genetic regions as sig...

Determining the genetic architecture of Alzheimer’s disease pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we perform a genome-wide association study of cortical tau quantified by positron emission tomography in 3046 participants from 12 independent studies. The CYP1B1-RMDN2 locus is associated wit...

INTRODUCTION MicroRNAs are short non‐coding RNAs that control proteostasis at the systems level and are emerging as potential prognostic and diagnostic biomarkers for Alzheimer's disease (AD). METHODS We performed small RNA sequencing on plasma samples from 847 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. RESULTS We identified...

INTRODUCTION MicroRNAs (miRNAs) play important roles in gene expression regulation and Alzheimer's disease (AD) pathogenesis. METHODS We investigated the association between baseline plasma miRNAs and central AD biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 803): amyloid, tau, and neurodegeneration (A/T/N). Differentia...

Objective Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with a...

INTRODUCTION Alzheimer's disease (AD) initiates years prior to symptoms, underscoring the importance of early detection. While amyloid accumulation starts early, individuals with substantial amyloid burden may remain cognitively normal, implying that amyloid alone is not sufficient for early risk assessment. METHODS Given the genetic susceptibilit...

A synaptic protein, Neuronal Pentraxin 2 (NPTX2), has emerged as a pivotal biomarker for Alzheimer's dementia (AD). We identified candidate miRNAs targeting NPTX2 and performed association and mediation analyses using multi‐omics data (N = 702). Among 44 candidate miRNAs, miR‐133b was significantly associated with AD and Braak positivity. Higher mi...

Background Plasma neurofilament light chain (NfL) is a blood biomarker of neurodegeneration, including Alzheimer’s disease. However, its usefulness may be influenced by common conditions in older adults, including amyloid-β (Aβ) deposition and cardiometabolic risk factors like hypertension, diabetes mellitus (DM), impaired kidney function, and obes...