Sex differences in associations between APOE ε2 and longitudinal cognitive decline.

Introduction: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples.

Methods: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs.

Unified epigenomic, transcriptomic, proteomic, and metabolomic taxonomy of Alzheimer's disease progression and heterogeneity.

Alzheimer's disease (AD) is a heterogeneous disorder with abnormalities in multiple biological domains. In an advanced machine learning analysis of postmortem brain and in vivo blood multi-omics molecular data ( = 1863), we integrated epigenomic, transcriptomic, proteomic, and metabolomic profiles into a multilevel biological AD taxonomy. We obtained a personalized multilevel molecular index of AD dementia progression that predicts severity of neuropathologies, and identified three robust molecular-based subtypes that explain much of the pathologic and clinical heterogeneity of AD.

Spatial Extent of Amyloid-β Levels and Associations With Tau-PET and Cognition.

Importance: Preventive trials of anti-amyloid agents might preferably recruit persons showing earliest biologically relevant β-amyloid (Aβ) binding on positron emission tomography (PET).

Objective: To investigate the timing at which Aβ-PET binding starts showing associations with other markers of Alzheimer disease.

Design, Setting, And Participants: This longitudinal multicentric cohort study included 3 independent cohorts: Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) (data collected from 2012-2020), Alzheimer Disease Neuroimaging Initiative (ADNI) (data collected from 2005-2019), and Harvard Aging Brain Study (HABS) (data collected from 2011-2019).

Plasma p-tau231, p-tau181, PET Biomarkers, and Cognitive Change in Older Adults.

Objective: The objective of this study was to evaluate novel plasma p-tau231 and p-tau181, as well as Aβ and Aβ assays as indicators of tau and Aβ pathologies measured with positron emission tomography (PET), and their association with cognitive change, in cognitively unimpaired older adults.

Methods: In a cohort of 244 older adults at risk of Alzheimer's disease (AD) owing to a family history of AD dementia, we measured single molecule array (Simoa)-based plasma tau biomarkers (p-tau231 and p-tau181), Aβ and Aβ with immunoprecipitation mass spectrometry, and Simoa neurofilament light (NfL). A subset of 129 participants underwent amyloid-β ( F-NAV4694) and tau ( F-flortaucipir) PET assessments.

Healthy versus Entorhinal Cortical Atrophy Identification in Asymptomatic APOE4 Carriers at Risk for Alzheimer's Disease.

Early detection of Alzheimer's disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ɛ4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ɛ4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments.

'Alzheimer's Progression Score': Development of a Biomarker Summary Outcome for AD Prevention Trials.

Background: Alzheimer's disease (AD) prevention research requires methods for measurement of disease progression not yet revealed by symptoms. Preferably, such measurement should encompass multiple disease markers.

Objectives: Evaluate an item response theory (IRT) model-based latent variable Alzheimer Progression Score (APS) that uses multi-modal disease markers to estimate pre-clinical disease progression.

Effects of rs3846662 Variants on HMGCR mRNA and Protein Levels and on Markers of Alzheimer's Disease Pathology.

3-Hydroxy-3-methyglutaryl coenzyme A reductase (HMGCR) is a cholesterol-regulating gene with statin relevance. rs3846662 being involved in regulation of HMGCR alternative splicing, we explored its impact on HMGCR messenger RNA (mRNA) and protein levels in the brain and the associations between those levels and levels of Alzheimer's disease pathological markers. We used brain samples derived from a cohort of 33 non-demented controls and 90 Alzheimer's disease autopsied-confirmed cases.