The Genetic Landscape of Alzheimer’s disease

Amyloid precursor protein

In the amyloidogenic pathway, its proteolysis produces two variants of Aβ, one of which is aggredation prone and is found in AD brain plaques.

Presenilin 1 and 2

Mutations in these genes impair the γ-secretase mediated cleavage of APP. PSEN 1 mutations can have complete penetrance.

Apolipoprotein E

APOE encodes for ApoE which is involved in neuronal growth, repair response to injury, nerve regeneration, immunoregulation and activation of lipolytic enzymes.

There are three major allelic variants with APOE ε4 increasing the risk of both early and late onset AD. It does not cause the disease on its own.

TREM2

TREM2 codes for the triggering receptor expressed on myeloid cells and increses risk for late onset AD. It’s effect is comparable to that of APOE but its frequency is low.