The Role of Membrane Damage in Neurodegeneration

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Membrane damage has been implicated as an early pathogenic event in Alzheimer's Disease (AD). Recent genome-wide association studies (GWAS) have identified three broad fields of cellular function associated with increased risk of late-onset Alzheimer's Disease (LOAD): endocytosis, phospholipid metabolism and the innate immune system. Together, these demonstrate the importance of membrane integrity in AD.The endosomal sorting complex required for transport (ESCRT) pathway has an essential role in mediating membrane repair and has been implicated in neurodegeneration. Mutations in CHMP2B, a component of ESCRT complexes, causes a rare type of frontotemporal dementia (FTD). A further link has also recently been recognized with the identification of CD2-associated protein (CD2AP) as a risk gene for LOAD. CD2AP functions between cell membranes and the actin cytoskeleton and binds to the ESCRT complex via the ESCRT-I components ALIX and TSG101.