Systematic assessment of pathophysiological mechanisms and their interrelation in progression of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) consists of 60-80% of all dementia cases, thus is recognized as the commonest form of dementia. The current challenge to clinicians and researchers in the field of AD is development of treatment plans that can target the progression of pathology at molecular level as well newer diagnostic techniques for early detection and prevention of AD. This could be achieved by enhancing our understanding of the underlying pathophysiology of AD. This is systematic and concise review of various pathophysiological mechanisms contributing to AD. Legitimate indexing portals and search websites were used to carry out the literature search for this article. A combination of MeSH terms and Boolean operators were used. Obtained research articles were carefully assessed first by reading title and abstract and finally by reading the whole text. A set of inclusion and exclusion criteria were used to select the reference articles.: In our literature search 75 articles were obtained from PubMed, Google scholar and Cochrane Library after removing duplicate records. These were screened using titles and abstract. 23 articles were excluded from the study as per the exclusion criteria. Full text of 52 articles were read. 7 articles were excluded, 45 were studied thoughrouly and 30 were referenced during the writing of this review.Various risk factors – old age, diabetes, smoking, mutation etc contribute to Aβ plaque accumulation due to cleavage of APP protein by α and ϒ secretase. Aβ plaque further contributes to accumulation of neurofibrillary tangles, neuroinflammation and oxidative stress. This together with disturbance in Calcium homeostasis and excitotoxicity at glutamate receptors contribute to neurodegeneration and synaptic toxicity.