Genetics of early onset Alzheimer's disease

Published on August 26, 2010 Reviewed on April 12, 2022   35 min

A selection of talks on Clinical Practice

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EKATERINA ROGAEVA: Hello. My name is Ekaterina Rogaeva. And I will present the data about the genetics of early-onset form of Alzheimer's disease which is considered to be highly familial.
We will talk about contribution of APP, PSEN1, and PSEN2 in the early-onset form of the disorder. We will also try to understand why these mutations lead to Alzheimer's disease. We'll talk phenotypic variability in early-onset disease and also genetic testing for Alzheimer's disease in clinical practice.
But first, I have to make a few general points about Alzheimer's disease, which is the most common form of progressive dementia. The brain pathology is characterized by neuronal loss, eventually leading to severe brain atrophy. Accumulation of the protein called amyloid, beta-peptide, or A beta in the form of extracellular amyloid plaques is the earliest sign of the brain pathology related to Alzheimer's disease. And finally, the disease pathology also associated is the deposition of tau positive neurofibrillary tangles inside of neurons. Clearly the formation of tangles has neurotoxic consequences itself because mutations in this gene are responsible for frontotemporal dementia. However, currently there is no convincing data that tau is genetically involved in early-onset form of Alzheimer's disease.
Neurotoxic A. Beta peptides are generated by cleavage of amyloid precursor protein known as APP. It is a type 1 membrane protein, a fragment of which accumulates in Alzheimer's disease brain. Accumulation of amyloid plaques starts decaying prior to disease symptoms and precedes the tau pathologen.