Dementia Awareness Week: Alzheimer's Research & Therapy joins the discussion

This week is the Alzheimer’s Society’s Dementia Awareness Week and Alzheimer’s Research & Therapy is talking about the impact of genetic variants on Alzheimer’s disease (AD).

AD is the most common form of dementia in older people and is characterized by behavioral disorders and a progressive decline in memory function. Genetic studies have provided the best evidence for cause and effect relationships in AD, and recent years have seen tremendous progress in genetics technology to allow for full individualized genomic screening across populations and within individuals.

Examples of the advances include identification of mutations in APP, PSEN1 and PSEN2 genes, which provided a link to the characteristic amyloid plaques seen in AD brains and supported the amyloid cascade hypothesis. Also, studies of the apolipoprotein E (APOE) gene indicated that mutations of the ε4 allele are responsible for approximately one-third of the population-attributable risk for the disease.

Very recently, two large consortiums demonstrated that rare variants in the TREM2 gene (a type 1 membrane receptor protein primarily expressed on microglia in the central nervous system that has been shown to regulate phagocytosis and activation of monocytes) confers significant risk for AD. The association of TREM2 variants with AD highlights innate immunity’s role as a significant factor in AD pathogenesis.

In a new review published today for Alzheimer’s Research & Therapy, Editor-in-Chief Todd Golde highlights TREM2’s importance: “With the spotlight firmly placed on TREM2’s role in AD, research advances will likely be quite rapid, and the emerging data will likely enable a more unified understanding of the function of innate immune signalling in AD.

TREM2 never reached genome-wide significance in the published genome-wide association studies. Thus, combining biological inference with whole exome or whole genome sequencing strategies is likely to yield a treasure chest of novel genetic variants in innate immune signalling factors that influence risk for AD. Hopefully, these will not only tell us more about AD pathogenesis, but will also reveal tractable therapeutic targets”

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