Tutun Das AKA, Mamun Or RASHID, Shujit Chandra PAUL, Abdul HALİM

A review on molecular neuropathology of Alzheimer’s disease in association with aging

Alzheimer’s disease (AD) is a chronic neurodegenerative disease where learning and memory deficit occur. Aging is the main culprit responsible for this disease. Many hypotheses have been proposed for explaining the neuropathology of AD. Amyloid cascade hypothesis states that AD may cause due to neuronal damage by forming senile plaque of beta amyloid (Aβ) and followed by the formation of neurofibrillary tangles (NFTs). Due to mismetabolism of amyloid precursor protein (APP), Aβ aggregates and initiates AD. Mitochondrial cascade hypothesis emphasize on mitochondrial dysfunction in aged brain which starts by rising Aβ accumulation, later tau hyperphosphorylation and inflammation, and finally development of AD. According to the calcium hypothesis, dysregulation of neuronal Ca²+ signaling incurs apoptosis of neuronal cells that interrupts cognitive functions and initiates AD. Tau hypothesis propose that aggregation of tau protein may lead the formation of NFTs which is a pathological hallmark of AD. Oxidative stress hypothesis states that brain aging increase the production of lipid peroxides and reactive oxygen species by elevating oxidative stress level which causes AD. In aged brain, accumulation of oxysterol due to impairment of Blood Brain Barrier (BBB) may lead to formation of AD which is purported in cholesterol hypothesis. Again, neuroinflammation hypothesis says that immune system’s cell injury occurs in AD which plays a dominating role in AD inflammation. However, the mechanism of neuropathology of AD remains poorly understood still now. This review critically evaluates different hypotheses which may become helpful for the future researchers to scrutinize more acceptable molecular neuropathology of AD.

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