Abstract

ALZHEIMER’S DISEASE: RECENT INSIGHTS INTO MOLECULAR PATHOGENESIS AND GENETICS

Anjana George*

ABSTRACT

Alzheimer’s disease is a progressive, neurodegenerative disease that represents a growing global health crisis. AD is the most common cause of dementia in older adults, with an increasing incidence as a function of age. It is associated with cognitive, functional, behavioural impairments, and is characterized by two underlying pathological hallmarks: the progressive accumulation of extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). The two major types of the disease are early-onset or familial and late-onset or sporadic forms. Genetic factors have been linked to both early and late-onset AD. Mutations in APP, PSEN1 or PSEN2 lead to overproduction of pathological Aβ fragments and consequently to amyloid pathology with increased plaque formation. Alterations to chromosomes 1, 14, and 21 are associated with early-onset AD, whereas the presence of APOE- ε4 allele a form of the apolipoprotein E gene on chromosome 19 increases risk of developing late-onset AD. This review focus on the different molecular hypothesis of tau forming neurofibrillary tangles, amyloidogenic processing of amyloid precursor protein in forming amyloid plaques, interconnected molecular events involved in neuroinflammation and neurodegeneration, and insights on novel developments in the genetics of Alzheimer’s Disease.

Keywords: Alzheimer’s disease, Genetics, Amyloid ? plaques, Neurofibrillary tangles.