Biomarkers.

Background: Lewy body disease (LBD) often co-occurs with Alzheimer's disease neuropathological change (ADNC), which can be detected using plasma pTau181 and pTau217. Few studies have investigated these biomarkers in LBD, nor have studies investigated plasma pTau217 in Parkinson's disease (PD) cognitively normal patients (LBD-CN), or in alpha-synuclein positive (asyn-positive) participants. Furthermore, uncertainties remain regarding LBD-specific cut-points for these biomarkers.

Developing Topics.

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 variant analysis to identify novel genetic drivers of cognition in aging and disease.

Method: We leveraged 8 cohorts of cognitive aging with whole genome sequencing data from the AD Sequencing Project to conduct rare variant analyses of multiple domains of cognition (N = 9,317; mean age = 73; 56% female; 52% cognitively unimpaired).

Vascular risk factors and cerebrovascular pathologic changes on autopsy: The 90+ Study.

Introduction: Cerebrovascular pathologic changes (CVPC) are prevalent and associated with dementia in those ≥ 90 years. However, CVPC associations to traditional risk factors (hypertension, diabetes, and hyperlipidemia) are variable. We hypothesized that neither traditional risk factors nor related medications would be associated with CVPC presence.

regionalpcs improve discovery of DNA methylation associations with complex traits.

We have developed the regionalpcs method, an approach for summarizing gene-level methylation. regionalpcs addresses the challenge of deciphering complex epigenetic mechanisms in diseases like Alzheimer's disease. In contrast to averaging, regionalpcs uses principal components analysis to capture complex methylation patterns across gene regions.

Medical Histories Associated With Absence of Alzheimer Disease Neuropathologic Changes in the Oldest-Old: The 90+ Study.

Objectives: Exploration of medical histories and medications associated with Alzheimer disease neuropathologic change (ADNC) absence and potential resistance may identify protective factors against ADNC. This was a retrospective examination of data from participants age ≥90 years who enrolled in , a longitudinal study based in California. Participants underwent neuropathologic analysis for the presence of neuritic amyloid plaques (NPs) (any), beta amyloid plaques (Thal phase > 0), and neurofibrillary tangles (>2).