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SORL1 has been identified as a major contributor to late onset Alzheimer's disease (LOAD). We test whether genetic variability in the 5' of SORL1 gene modulates the risk to develop LOAD via regulation of SORL1-messenger ribonucleic acid (mRNA) expression and splicing. Two brain structures, different...

Background

A straightforward, reproducible blood-based test that predicts age dependent risk of Alzheimer's disease (AD) could be used as an enrichment tool for clinical development of therapies. This study evaluated the prognostic performance of a genetics-based biomarker risk algorithm (GB...
The molecular genetic basis that leads to Lewy Body (LB) pathology in 15-20% of Alzheimer disease cases (LBV/AD) was largely unknown. Alpha-synuclein (SNCA) and Leucine-rich repeat kinase2 (LRRK2) have been implicated in the pathogenesis of Parkinson's disease (PD), the prototype of LB spectrum diso...
The recruitment of asymptomatic volunteers has been identified as a critical factor that is delaying the development and validation of preventive therapies for Alzheimer disease (AD). Typical recruitment strategies involve the use of convenience samples or soliciting participation of older adults wi...

Background

We sought to determine if the APOE epsilon4 allele influences both the functional activation and connectivity of the medial temporal lobes (MTLs) during successful memory encoding in young adults.

Methods

Twenty-four healthy young adults, i.e., 12 carriers and 12 noncarrier...

Background

We investigated the genomic region spanning the Translocase of the Outer Mitochondrial Membrane 40-kD (TOMM40) and Apolipoprotein E (APOE) genes, that has been associated with the risk and age of onset of late-onset Alzheimer's disease (LOAD) to determine whether a highly polymorp...

Background

Alternative gene transcript splicing permits a single gene to produce multiple proteins with varied functions. Bioinformatic investigations have identified numerous splice variants, but whether these transcripts are translated to functional proteins and the physiological significa...
Numerous genome-wide screens for polymorphisms that influence gene expression have provided key insights into the genetic control of transcription. Despite this work, the relevance of specific polymorphisms to in vivo expression and splicing remains unclear. We carried out the first genome-wide scre...

Background

Understanding regional differences in cognitive performance is important for interpretation of data from large multinational clinical trials.

Methods

Data from Durham and Cabarrus Counties in North Carolina, USA and Tomsk, Russia (n = 2972) were evaluated. The Montreal Cogn...
If we are to find treatments to postpone, reduce the risk of, or completely prevent the clinical onset of Alzheimer disease (AD), we need faster methods to evaluate promising preclinical AD treatments, new ways to work together in support of common goals, and a determination to expedite the initiati...
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