Neurobiological Mechanisms Involved in the Pathogenesis of Alzheimer’s Disease

  • Fayaz Ahmad Mir
  • Zaigham Abbas RizviEmail author


Alzheimer’s disease (AD) is one of the many neurodegenerative disorders which is characterized by progressive loss of neurons due to the extracellular accumulation of misprocessed and aggregated amyloid beta (Aβ)-plaques and appearance of intracellular neurofibrillary tangles containing hyperphosphorylated tau protein which ultimately leads to loss of synapses and cognitive decline. Aggregation of amyloid beta (Aβ)-plaques is the hallmark of AD. Aβ is the proteolytic cleavage product of amyloid precursor protein (APP) which is cleaved by β- and γ-secretase enzymes into Aβ1–42 and Aβ1–40 isoforms where the former readily aggregate more rapidly than the latter. Tau protein, the major component of neurofibrillary tangles, is a microtubule-associated protein which is usually soluble but becomes insoluble as it forms tangles of oligomers which is thought to be initiated by toxic concentrations of Aβ-plaques. Recent studies have shown that some genetic mutations, genomic instability and other factors like head injuries, depression, imbalanced diet and age progression all contribute to the development and progression of AD. The most important gene, for which a role in ageing-related late-onset AD has been established since a decade, is APOE where different variants of the gene differently predispose the individuals to the development of AD. In this chapter, we will be highlighting well-established molecular and cellular mechanisms behind the development and progression of AD, the regions in the brain that are affected and the known genetic basis behind the onset and pathophysiology of AD. In the later section, we will address some of the current and prospective therapeutic interventions based on our current understanding of neurobiological mechanisms underlying AD.


Alzheimer’s disease Aβ-plaques Neurodegeneration Cytotoxicity Neuroinflammation tau protein Axonal transport 


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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.School of Life SciencesJawaharlal Nehru UniversityNew DelhiIndia
  2. 2.Centre for Microbial EcologyTranslational Health Science and Technology Institute, NCR Biotech Science ClusterFaridabadIndia

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