Carlos A. Pasqualucci

• University of São Paulo

Background Cognitive impairment and disability are frequent among the oldest-old population, particularly in low- and middle-income countries (LMIC), where this population is rapidly increasing. However, studies on people aged 90 or older are scarce in these settings. Here we analyze the characteristics of the Brazilian Very Old 90+ (BRAVO 90+) stu...

Background The Neuromodulatory Subcortical System (NSS) consists of nuclei exhibiting early vulnerability to tauopathies, including Alzheimer’s Disease (AD). Within the NSS, there is a spectrum of vulnerability that becomes apparent in the earliest stages of AD, offering a chance to probe factors underlying vulnerability to AD. Method In this stud...

Background Frailty, characterized by increased physical vulnerability, is associated with a higher incidence and severity of cognitive impairment and also a higher burden of neurodegenerative and cerebrovascular diseases. This study investigates the association between frailty and neurodegenerative and cerebrovascular pathologies. Method Cross‐sec...

Background Racial differences in dementia prevalence and incidence were found with higher dementia burden in African descendants. Previous neuropathological studies were conducted mostly in white participants in convenience samples. Further studies in diverse populations are important to foster the understanding of race differences in dementia path...

Background Hypertension is a midlife modifiable risk factor for dementia. Uncontrolled hypertension is related to brain damage that could result in cognitive impairment, and one way of evaluating uncontrolled hypertension through life is assessing left ventricular hypertrophy (LVH). Previous imaging studies have shown a relationship between LVH and...

Background Nitric oxide (NO) is involved in synaptic transmission and cerebral plasticity, playing a role in the memory process. However, in states of brain inflammation, hypoxia, or ischemia, there is induction of inducible nitric oxide synthase (iNOS) expression by astrocytes and pyramidal cells in the brain. Under conditions of chronic activatio...

Background Previous studies suggest an association between Alzheimer’s disease and carotid artery atherosclerosis. However, the association between atherosclerotic carotid plaque composition and Alzheimer’s disease pathology (neuritic plaques and neurofibrillary tangles) has not been explored yet. Method Carotid arteries were dissected and the seg...

Background Alzheimer’s Disease(AD) patients experience circadian rhythm disorder. The circadian rhythm is synchronized by a master clock, the suprachiasmatic nucleus(SCN), which is spatially well‐conserved but a tiny nucleus in the hypothalamus. Little is known about the molecular and pathological changes that occur in the SCN during AD progression...

Background Transactive DNA‐binding protein 43 (TDP‐43) proteinopathy is associated with neurodegeneration, including LATE and linked to cognitive deterioration. While some research suggests a higher prevalence of TDP‐43 in women, no differences have been identified among racial groups. Nonetheless, the influence of gender on cognition within the co...

Background The atherosclerotic plaque in carotid arteries has been associated with dementia. Clinic radiological studies in older adults suggest that the composition of atherosclerotic plaque in the carotid artery can predict vascular dementia (VD) or mixed dementia. The proposed study aims to assess components of atherosclerotic plaques in the car...

Background Excessive daytime sleepiness is a common and early symptom of Alzheimer’s disease (AD). The subcortical wake‐promoting neurons in the lateral hypothalamic area, tuberomammillary nucleus (TMN), and locus coeruleus synchronize to maintain wakefulness/arousal. Although significant neuronal decline occurs in wake‐promoting regions, the TMN h...

Background Lewy body disease (LBD) is a neurodegenerative condition marked by the accumulation of neuronal alpha‐synuclein, leading to both Parkinson’s disease and Lewy body dementia. It is regarded as the second most common neurodegenerative disease associated with aging. However, there is limited knowledge of LBD prevalence in the general populat...

Background The study of dementia and its differences between the sexes is widely investigated, mainly in Alzheimer’s disease. However, most studies on dementia are not carried out in a multiethnic population. Here we analyze demographic data, clinical symptoms, and neuropathological characteristics of a large mixed Brazilian sample. Method The Bio...

Background Prior research investigating sex and racial differences in amyloid pathology burden has yielded inconsistent findings. We examined the impact of sex and other confounding factors on neuritic plaque burden and cognitive outcomes. Method This study included 1,857 individuals, with post‐mortem brain tissues, from the Biobank for Aging Stud...

Background Clinicopathological studies suggest a role of minor cerebrovascular changes in the cognitive decline of individuals with a low neurodegenerative burden. However, it remains unclear whether small vascular brain lesions can impact cognition in middle aging individuals. Additionally, recent clinicopathological studies have shown that even a...

Background The association of moderate and severe dementia with low body mass index (BMI) is well described, but weight decline seems to also occur in individuals with preclinical neuropathologies. Considering that up to one-fifth of individuals with normal cognition meet the criteria for a dementia-related neuropathological diagnosis, autopsy stud...

Importance Race differences in dementia prevalence and incidence have previously been reported, with higher dementia burden in Black decedents. However, previous neuropathological studies were conducted mostly in convenience samples with White participants; conducting clinicopathological studies across populations is crucial for understanding the u...

Background Depression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD)...

Background: Sleep-wake dysfunction is an early and common event in Alzheimers disease (AD). The lateral hypothalamic area (LHA) regulates the sleep and wake cycle through wake-promoting orexinergic and sleep-promoting melanin-concentrating hormone (MCH) neurons. These neurons share close anatomical proximity with functional reciprocity. This study...

Individuals with Alzheimers Disease (AD) experience circadian rhythm disorder. The circadian rhythm is synchronized by a master clock, the suprachiasmatic nucleus (SCN), which is a tiny hypothalamic nucleus. Little is known about the molecular and pathological changes that occur in the SCN during AD progression. We examined postmortem brains of 12...

Background Coronary heart disease (CHD) is the leading cause of mortality worldwide. Dementia is also among the ten most common causes of mortality, and it is one of the main causes of disability in older people. However, the association of direct morphometric percentage of obstruction in coronary arteries with Alzheimer’s disease (AD) type‐patholo...

Background Sleep/wake disturbance is a common and debilitating symptom of Alzheimer’s disease (AD) that precedes cognitive loss. The lateral hypothalamic area (LHA) is critical in orchestrating the sleep/wake cycle through the neuropeptide orexin and melanin‐concentrating hormone. We previously demonstrated that LHA neurons accumulate AD‐tau from B...

Background The presence of aging‐related tau astrogliopathy (ARTAG) is highly frequent, but poorly characterized in aging brain and neurodegeneration. Over the abnormal tau accumulation processes, tau protein undergoes pathological modifications and the sequency of these pathological events can be associated with different levels of tau aggregation...

Background Although Alzheimer’s disease (AD) etiology is partially explained by the deposition of aggregated forms of β‐amyloid proteins and neurofibrillary tangles in the brain, the process that triggers the deposition of these proteins is still unknown. The neural (nNOS), endothelial (eNOS), and inducible nitric oxide synthases (iNOS) may play an...

Background The APOE gene is identified as a major risk factor for late onset Alzheimer’s disease and has three alleles, ε2, ε3 and ε4, related to two non‐synonymous substitutions. The presence of the ε4 allele confers an increased risk for the disease in a dose dependent manner (odds ratio 12.9 for homozygous individuals and between 3.2 and 4.2 for...

Background The two main catecholaminergic members of the isodendritic core nuclei are the substantia nigra (SN) and the locus coeruleus (LC). Despite cytoarchitectural and neurochemical similarities between the two nuclei, the LC is significantly more vulnerable to early degenerative changes in tauopathies like Alzheimer’s disease (AD) as compared...

Background Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease predominantly found in former athletes and associated with repetitive brain injury (TBI). Despite the increased number of studies, several questions about prevalence and risk factors for CTE in the general population remain unknown. Method to investigate t...

Background A biological mechanism in cancer promotion may have a protective role against AD ¹ . Although disparities between the clinical and the anatomopathological postmortem diagnoses related to the etiology of dementia and cancer were described ² , most previous studies were based only on the clinical diagnoses for both diseases. Therefore, we...

Background Alzheimer’s Disease (AD) patients commonly experience sleep/wake (S/W) disturbances, such as sleep fragmentation and excessive daytime sleepiness. The S/W cycle is controlled by a complex system regulated by a master regulator, the suprachiasmatic nucleus (SCN) that controls wake‐ and sleep‐promoting nuclei. Despite its importance in orc...

Background Given the progressive nature of neurodegenerative pathologies, great effort has been made to create diagnostic tools for detecting neurodegenerative changes in their early stages. However, the lack of information about the frequency of neurodegenerative changes in mid‐age adults impacts biomarker interpretation and sensitivity improvemen...

Background The association between moderate/severe dementia and lower Body Mass Index (BMI) is well described, but the weight decline seems to also occur in cognitively normal individuals with preclinical dementia. Considering that up to one‐fifth of individuals with normal cognition might meet the criteria for a neuropathological diagnosis, autops...

Background Apolipoprotein E ε4 allele (APOE‐ε4) is the main genetic risk factor for dementia. APOE‐ε4 is also associated with Alzheimer’s disease (AD) pathology, cerebrovascular disease, and non‐AD neurodegenerative pathologies. Although APOE‐ε4 may influence cognitive impairment through these pathways, less evidence is available from diverse popul...

Background Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer’s disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to e...

Atypical Alzheimer's disease shares similar neuropathological changes with amnestic AD, i.e., accumulation of extracellular amyloid-beta plaques and aggregation of intracellular tau tangles; however, atypical AD presents different symptoms and patterns of brain atrophy. Thus, contrasting amnestic and atypical AD provides a unique framework to inves...

Introduction: Apolipoprotein E (APOE) ε4 allele has been associated with higher carotid atherosclerosis risk, while the APOE-ε2 seems to decrease this risk. Data from autopsy studies, where carotid arteries can be evaluated in their full extension, is scarce. Therefore, we investigated the association between APOE alleles and direct morphometric m...

Background Neuropsychiatric symptoms (NPS) are very common in Lewy body dementias (LBD), but their aetiology is poorly understood. In a post‐mortem study we aimed to characterise the contribution of neuropathological substrates to some of the most common NPS in dementia. Method Participants who passed away between 2004 and 2021 underwent comprehen...

Background: Studying the effects of smoking intensity is important to evaluate the risk of tobacco use on a range of illnesses, such as as sarcopenia among the elderly. Thus, this study aimed to analyze the effects of pack-years of cigarette smoking on the diaphragm muscle (DIAm) histopathology of postmortem samples. Methods: Subjects were divid...

Bipolar disorder (BD) presents with a progressive course in a subset of patients. However, our knowledge of molecular changes in older BD is limited. In this study, we examined gene expression changes in the hippocampus of BD from the Biobank of Aging Studies to identify genes of interest that warrant further exploration. RNA was extracted from the...

Background Coronary atherosclerosis assessed in vivo was associated with cognitive impairment; however, conflicting findings have been reported in autopsy samples. Objective Our aims were to assess the association between atherosclerotic stenosis in the coronary arteries and cognitive impairment and to investigate the possibility of selection bias...

The human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. W...

Diabetes mellitus (DM) is an important risk factor for dementia, which is a common neurodegenerative disorder. DM is known to activate inflammation, oxidative stress, and advanced glycation end products (AGEs) generation, all capable of inducing neuronal dysfunctions, thus participating in the neurodegeneration progress. In that process, disturbed...

Background: Education is believed to contribute positively to brain structure and function, as well as to cognitive reserve. One of the brain regions most impacted by education is the medial temporal lobe (MTL), a region that houses the hippocampus, which has an important role in learning processes and in consolidation of memories, and is also kno...

Dementia affects more Black individuals, likely due to a combination of environmental and biological factors1,2,3. APOE ε4 allele risk of dementia is different between individuals with European (EUR) and African (AFR) ancestries4,5,6. It is unclear what drives these differences in Alzheimer’s disease (AD) neuropathology among patients with cognitiv...

Background Most people with dementia already live in low‐ to middle‐income countries (LMIC). However, most evidence regarding dementia prevention comes from high‐income countries that have different socioeconomic status (SES) and risk factors prevalence than LMIC. In this session, we will present results on risk and protective factors for dementia...

Introduction: Neuropsychiatric symptoms (NPS) are common in Lewy body disease (LBD), but their etiology is poorly understood. Methods: In a population-based post mortem study neuropathological data was collected for Lewy body (LB) neuropathology, neurofibrillary tangles (NFT), amyloid beta burden, TDP-43, lacunar infarcts, cerebral amyloid angio...

Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE ε4 risk of dementia in African ancestry (AFR), but a dearth of neuropathological data preclude the interpretation of the biological factors underlying these findings...

Background : Apolipoprotein E gene (APOE) ε4 allele is associated with a higher risk of carotid atherosclerosis, but less is known about the association of APOE with intracranial atherosclerotic disease (IAD). We aimed to investigate the association of APOE alleles with IAD in a cross-sectional autopsy study. Methods : We measured the stenosis in...

Aims Mitochondrial (mt) DNA replication is strongly associated with oxidative stress, a condition triggered by aging and hyperglycemia, both of which contribute to mitophagy disruption and inflammation. This observational exploratory study evaluated mtDNA-copy number (mtDNA-CN) and expression of genes involved in mitochondriogenesis (PPARGC1A, TFAM...

Objective: To establish a microcephaly cut-off size in adults using head circumference as an indirect measure of brain size, as well as to explore factors associated with microcephaly via data mining. Methods: In autopsy studies, head circumference was measured with an inelastic tape placed around the skull. Total brain volume was also directly...

Associations between age-related neuropathological lesions and adult-onset lifetime major depressive disorder (a-MDD), late-life MDD (LLD), or depressive symptoms close to death (DS) were examined in a large community sample of non-demented older adults. 741 individuals (age at death=72.2±11.7 years) from the Biobank for Aging Studies were analyzed...

Background Inflammation of the perivascular adipose tissue (PvAT) may be related to atherosclerosis; however, the association of polarized macrophages in the pericoronary PvAT with measurements of atherosclerosis components in humans has not been fully investigated. Methods and Results Coronary arteries were dissected with surrounding PvAT. We eva...

Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE ϵ4 risk of dementia in African ancestry (AFR), but lack of neuropathological data preclude the interpretation of the biological factors underlying these findings, in...

Raman spectroscopy was used to identify biochemical differences in normal brain tissue (cerebellum and meninges) compared to tumors (glioblastoma, medulloblastoma, schwannoma, and meningioma) through biochemical information obtained from the samples. A total of 263 spectra were obtained from fragments of the normal cerebellum (65), normal meninges...

Objective: This study aimed to compare causes of death in the most prevalent neuropathologically diagnosed dementias. Methods: We analyzed causes of death in a community-based cohort of participants aged 50 or older, submitted to full-body autopsy and a comprehensive neuropathologic examination of the brain. Individuals with Alzheimer disease (A...

Introduction: Education, and less frequently occupation, has been associated with lower dementia risk in studies from high-income countries. We aimed to investigate the association of cognitive impairment with education and occupation in a low-middle-income country sample. Methods: In this cross-sectional study, cognitive function was assessed b...

Background Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expre...

Background Clinical Dementia Rating Scale (CDR) is one of the most used assessment scales in the care of dementia but it still lacks a detailed analysis of construct validity. We aimed to analyze evidences of construct validity of the CDR to assess the level of cognitive decline by informants. Method We analyzed 650 records of elderly subjects bel...

Introduction: B-lymphocyte density in the pericoronary adipose tissue (PvAT) was correlated with plaque size in human coronary arteries. However, the subtypes of B cells in the PvAT and atherosclerotic plaque composition have not investigated yet. Hypothesis: We hypothesized that B2 and the ratio of B2/B1-like lymphocytes in the PvAT will correlate...

Background Inflammation in the perivascular adipose tissue (PvAT) might play a role in coronary artery disease. The T helper 1 (Th1) lymphocytes are the most popular T helper (Th) lymphocytes in atherosclerotic plaques and are proatherogenic. However, the association between the Th1 and Th lymphocytes in the PvAT with coronary atherosclerosis compo...

Objective To describe the postmortem neuropathological findings of a patient with Kufor Rakeb Syndrome (KRS) due to ATP13A2 mutation. KRS is characterized by juvenile-onset, levodopa-responsive parkinsonism associated with pyramidal signs, supranuclear gaze palsy, and cognitive impairment. Methods Detailed neuropathological analysis of the brain....

Background: Body mass index (BMI) in midlife is associated with dementia. However, the association between BMI and late-life obesity is controversial. Few studies have investigated the association between BMI and cognitive performance near the time of death using data from autopsy examination. We aimed to investigate the association between BMI and...

Objective: We aimed to evaluate, by immunohistochemistry, astrocytes, tyrosine hydroxylase (TH) and structural proteins expression (neurofilaments and microtubules — MAP2) changes in postmortem brain samples of individuals with Lewy body pathology. Methods: Braak PD stage≥III samples, classified by neuropathology analysis, from The Biobank for Agi...

The choroid plexus (CP) is an important structure for the brain. Besides its major role in the production of cerebrospinal fluid (CSF), it conveys signals originating from the brain, and from the circulatory system, shaping brain function in health and in pathology. Previous studies in rodents have revealed altered transcriptome both during aging a...

The novel Coronavirus disease (COVID-19) is responsible for thousands of deaths worldwide, especially in Brazil, currently one of the leading countries in number of infections and deaths. The beginning of the COVID-19 epidemic in Brazil is uncertain due to the low number of tests done in the country. The excess number of deaths can suggest the begi...

Alzheimer’s disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus—brain...

Background To investigate epigenetic mechanisms potentially involved in the cognitive decline associated with chronic alcohol intake, we evaluated the expressions of three micro‐RNAs (miR‐34a, ‐34b, and ‐34c) highly expressed in the hippocampus and involved in neuronal physiology and pathology. MiR‐34a participates in functioning and survival of ma...

Background Chronic traumatic encephalopathy (CTE) is a tauopathy associated with repeated brain injuries. The presence of co‐pathologies is not uncommon in individuals with CTE. Here, we described clinical and neuropathological findings of amateur soccer with a history of progressive parkinsonism and dementia. Method 63‐years old male with no fami...

Background The cerebellum has not been extensively studied in the setting of Alzheimer’s disease (AD). As the disease progresses, the cerebellum is one of the last brain regions to accumulate β‐amyloid (βA) deposits usually as diffuse plaques. However, distinct morphologies are described in the cerebellum in early‐onset Alzheimer’s disease (EOAD)....

Background Clinical symptoms in early‐onset dementia occurs before than 65 years of age and represents around 10% of the dementia cases. The evidence of tau lesions in young individuals from nonselected autopsy studies supports that AD‐type pathology can start much earlier than previously thought. However, the majority of studies in dementia are fo...

Background: The choroid plexus (CP) is an important structure for the brain. Besides its major role in the production of cerebrospinal fluid (CSF), it conveys signals originating from the brain and from the circulation, therefore shaping brain function in health and in pathology. In accordance, previous studies in rodents revealed altered transcrip...

Background : Depression has been associated with dementia. This study aimed to verify if β-amyloid Alzheimer's disease-type burden was associated with lifetime major depressive disorder (MDD) and with current depressive symptoms in a large population-based autopsy study. Methods : We included 1,013 deceased subjects submitted to autopsy (mean age=...

The differences in the biochemistry of normal and cancerous tissue could be better exploited by Raman spectroscopy when the spectral information from normal tissue is subtracted from the abnormal tissues. In this study, we evaluated the use of the normal-subtracted spectra to evidence the biochemical differences in the pre-cancerous and cancerous s...

Background/aims: Cigarette smoking is a key factor in systemic inflammation and oxidative stress, and it has also been associated with the loss of muscle strength and an elevated risk of pulmonary diseases. Thus, this study aimed to analyze the effects of cigarette smoking on the diaphragm muscle structure of postmortem samples. Methods: Immunoh...

Alzheimer's disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus - bra...

Sarcopenia is characterized as aging-related weakness and atrophy, which decreases the diaphragm force generating capacity leading to a decrease of expulsive non-ventilatory motor behaviors, which are critical for airway clearance. Thus, this study aimed to analyze the histopathology of the diaphragm in postmortem samples. Thirty individuals were i...

Background Macrophages and T lymphocytes in the perivascular adipose tissue (Pv AT ) were previously linked to coronary artery disease. However, the role of these cells and B lymphocytes in the human Pv AT adjacent to unstable atherosclerotic plaques has not been investigated. Moreover, previous studies were inconclusive on whether Pv AT inflammati...

Thank you for the opportunity to respond to the letter of Drs. Dani and Pittella concerning our recently published article “Neuropathological lesions in the very old: results from a large Brazilian autopsy study” (5). In this work analyzing the distribution of common neuropathological lesions associated with cognitive decline in individuals who die...

Background/aims: Smoking is a major risk factor for several cardiovascular and pulmonary diseases, and it has also been associated with the loss of skeletal muscle mass and strength leading to sarcopenia. The aim of this is study is to analyze the effects of cigarette smoking on the diaphragm muscle histopathology of postmortem samples from patien...

Abstract Analysis of the Raman data to obtain results in discrimination models is usually done with multivariate statistics based on principal component analysis (PCA). In this work, we present a technique based on a non-classical logic called paraconsistent logic (PL). The aim of this work is to use computational procedures capable of generating e...

Background: The relationship between cognitive impairment and abdominal visceral is controversial. Moreover, all studies so far used imaging studies to evaluate visceral fat and this association has not been described yet using autopsy material, which allows the direct quantification of abdominal fat. We aimed to investigate the association between...

Objective To compare neuropathological correlates of cognitive impairment between very old and younger individuals from a Brazilian clinicopathological study. Methods We assessed the frequency of neuropathological lesions and their association with cognitive impairment (Clinical Dementia Rating scale≥0.5) in the 80 or over age group compared to yo...

Background Behavioral and psychological symptoms (BPSD) can be a prodrome of dementia, and the Neuropsychiatric Inventory (NPI) is widely used for BPSD evaluation. Objective To compare the prevalence of BPSD according to cognitive status, and to determine NPI cutoffs that best discern individuals with mild cognitive impairment (MCI) and dementia f...

Many studies have been conducted to evaluate the association between air pollution and adverse health effects using a wide variety of methods to assess exposure. However, the assessment of individual long-term exposure to ambient air pollution is a challenging task and has not been evaluated in a large autopsy study. Our goal was to investigate whe...

Neurobiological models have provided consistent evidence of the involvement of cortical–subcortical circuitry in obsessive–compulsive disorder (OCD). The orbitofrontal cortex (OFC), involved in motivation and emotional responses, is an important regulatory node within this circuitry. However, OFC abnormalities at the cellular level have so far not...

Objectives The clinical symptoms of Alzheimer’s disease (AD) are preceded by a long asymptomatic period associated with “silent” deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The d...