Neuropathology of AD Sample Clauses

Neuropathology of AD. Microscopically, AD is characterised by the presence of extracellular cortical ‘plaques’ containing amyloid beta (Aβ) and intracellular ‘tangles’ containing hyperphosporylated tau protein in the brain, granulo-vacuolar degeneration, and eosinophilic rod-like inclusions (Perl, 2010) (Figure 1.1A,B). Cortical plaques are mainly composed of Aβ, which is a 4-kDa protein with a beta-pleated sheet configuration. It is derived from the fragmentation of the highly conserved transmembrane amyloid precursor protein (APP) which, upon the action of secretases, is cleaved into a 42–amino acid chain (Aβ 1–42), which is deposited within senile plaques and a 40–amino acid chain (Aβ 1–40), which tends to localise in cerebral cortical and cerebellar blood vessels (Xxxxxx et al., 1988). Neurofibrillary tangles are usually present as paired helical filaments, the main component of which is a hyperphosphorylated version of the microtubule-associated protein tau. The extent and distribution of these tangles within the brain has been shown to be indicative of the severity and duration of the disease (Xxxxxxxxx et al., 1992; Xxxxxx et al., 1995). Although neurofibrillary tangles are considered to be a clinical hallmark for AD, they are also observed in other neurodegenerative diseases, including post-traumatic dementia, dementia pugalistica, amyotrophic lateral sclerosis/parkinsonism dementia complex of Guam and post-encephalitic parkinsonism, as well as, the lysosomal storage disorder, Xxxxxxx-Pick disease, type C (Perl, 2010). In 1991, Xxxxx Xxxxx established a staging method for tracking AD progression through tau pathology. The presence of neurofibrillary tangles in the transentorhinal region of the brain is typical of Braak stages I and II, whilst stages III and IV are representative of tangle presence in the limbic regions including the hippocampus. Finally, Braak stages V and VI are indicative of more severe pathology, with tangles being present also in the neocortical regions (Braak and Braak, 1991).
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