Resumo

CARVAJAL CARVAJAL, Carlos. Biología molecular de la enfermedad de Alzheimer. Med. leg. Costa Rica [online]. 2016, vol.33, n.2, pp.104-122. ISSN 2215-5287.

Alzheimer disease (AD is a progressive neurodegenerative disease associated with cognitive decline and is the most common form of dementia in the enderly. A large number of factors has been associated with increased risk of AD, however, age represents, by far, the single greatest risk factor in the etiology of AD. The strongest common genetic variant for typical late-onset AD is apoliprotein E (APOE). Rare mutations in three genes have been implicated in familial early-onset disease: APP, PSEN1, and PSEN2.

Extracellular amyloid plaques and intraneuronal neurofibrillary tangles (NFT) are two major hallmark lesions of this fatal pathology.

Tau protein is involved in microtubule assembly and stabilization. Abnormal phosphorylation of tau, a prominent feature of AD brain, decreases its microtubule binding ability, which may destabilize microtubules and results in cellular damage.

A heterogeneous pool of monomeric Aβ peptide varying in length from 37 to 43 amino acids is generated from the transmembrane amyloid precursor protein (APP) by β- and ץ-secretase-mediated cleavage. The Aβ monomer has a high tendency to self-assemble into large aggregates and fibrils.

A diverse “Aβ oligomeric soup” exists, consisting of a large variety of rapidly exchangeable polymorphs that differ in size, conformation, intrinsic disorder, and toxicity.

Growing evidence suggests that the most detrimental forms of amyloid β peptides are the soluble oligomers and that the insoluble amorphous or fibrillar deposits represent a less harmful inactivated form of the peptide.

Several mechanisms have been proposed to account for abnormalities in AD, including Aβ toxicity, axonal transport deficiencies, and oxidative stress.

Palavras-chave : Alzheimer disease; amyloid plaques; amyloid beta; tau protein; neurodegenerative disorders; oxidative stress.

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