Abstract

RIBEIRO, Helem F.; DOS SANTOS, Jéssica Scarlet F  and  DE SOUZA, Julyanne N. Early-onset Alzheimer’s Disease (EOAD): neuropathological characteristics and associated genetic variants. Rev Neuropsiquiatr [online]. 2021, vol.84, n.2, pp.113-127. ISSN 0034-8597.  http://dx.doi.org/10.20453/rnp.v84i2.3998.

The most common neurodegenerative disease in the world is Alzheimer’s Disease (AD). Ten percent of Alzheimer patients experience symptoms before the age of 65, and almost all of them present genetic features of autosomal dominant inheritance nature, and penetrance of 92 to 100%. In the present review, we searched for genetic variants associated with early onset Alzheimer's disease (EOAD), emphasizing the most important characteristics and the main mutations. The genes most commonly related to the onset of EOAD are APP, PSEN1, PSEN2 and MAPT, whose mutations affect the metabolism and structure of these proteins. This process results in accumulations of Aβ peptide that leads to activation of the microglia and release of neurotoxic and pro-inflammatory factors that accelerate neurodegeneration. The PSEN1 gene is responsible for 70% of the known mutations in EOAD, while L166P is associated with below 30 years as the starting age of occurrence. APP mutations lead to protein aggregation in neurodegenerative plaques. All of the mutations described for MAPT are associated with an increase in neurofibrillary tangles. The E4 polymorphism of Apolipoprotein E (APOE) influences an increased risk of EOAD increasing up to three times the chances for heterozygous, and between eight and ten times for homozygotes carriers. Only 5% of the mutations associated with EOAD are known; new studies will show other candidate genes, as well as the importance of epigenetic factors changes in the etio-pathogenesis of this disease.

Keywords : Early-onset Alzheimer’s Disease; Amyloid beta-Peptides; Presenilin; Apolipoprotein E4; Tau protein; Mutation.

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