Biological Signatures of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the most prevalent and severe neurodegenerative disease affecting more than 0.024 billion people globally, more common in women as compared to men. Senile plaques and amyloid deposition are among the main causes of AD. Amyloid deposition is considered as a central event which induces the link between the production of β amyloid and vascular changes. Presence of numerous biomarkers such as cerebral amyloid angiopathy, microvascular changes, senile plaques, changes in white matter, granulovascular degeneration specifies the manifestation of AD while an aggregation of tau protein is considered as a primary marker of AD. Likewise, microvascular changes, activation of microglia (immune defense system of CNS), amyloid-beta aggregation, senile plaque and many more biomarkers are nearly found in all Alzheimer’s patients. It was seen that 70% of Alzheimer’s cases occur due to genetic factors. It has been reported in various studies that apolipoprotein E(APOE) mainly APOE4 is one of the major risk factors for the later onset of AD. Several pathological changes also occur in the white matter which include dilation of the perivascular space, loss of axons, reactive astrocytosis, oligodendrocytes and failure to drain interstitial fluid. In this review, we aim to highlight the various biological signatures associated with the AD which may further help in discovering multitargeting drug therapy.

TSPO Ligands PK11195 and Midazolam Reduce NLRP3 Inflammasome Activation and Proinflammatory Cytokine Release in BV-2 Cells

“…Microglial activation-induced neuroinflammation plays a vital role in the progression of neurodegenerative diseases, including AD (Sharma et al, 2020), PD (L'Episcopo et al, 2018), and perioperative neurocognitive disorders (PNDs; Saxena and Maze, 2018). In this study, BV2 microglial cells were activated by LPS, but the activation was significantly down-regulated with TSPO ligands.…”

Pathological Mechanisms Linking Diabetes Mellitus and Alzheimer’s Disease: the Receptor for Advanced Glycation End Products (RAGE)

“…Cognitive dysfunction has been documented as one of the complications of diabetes, suggesting a close link between diabetes and AD (Jash et al, 2020). One of the main symptoms of AD is impaired memory (Sharma et al, 2020); therefore, to test whether the memory is altered in mice after the injection of AGEs, we conducted the Morris Water Maze, Ymaze, and open field tests and found that the memory of AGE mice decreased significantly and anxiety behavior increased, which is consistent with previous AD research (Tian et al, 2019;Du et al, 2020). Subsequently, to further study whether the brain of AGE mice can develop AD symptoms, we assessed the expression of AD-related proteins such as P-tau and APP, which were significantly increased in the hippocampus of AGE mice.…”

Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer’s Disease

“…As stated earlier, atypical production and accumulation of Aβ peptides in the brain are considered as the hallmark of AD ( Al Mamun et al., 2020a ; Sharma et al., 2020 ; Uddin et al., 2020i ). Exogenous cannabinoids, a neuroprotective agent, have persistently been disclosed to restrain memory deficits in Aβ-treated animal models for both synthetic selective cannabinoid receptors agonists ( Haghani et al., 2012 ; Wang et al., 2013 ), as well as mixed cannabinoid receptors agonists ( Ramírez et al., 2005 ; Martín-Moreno et al., 2011 ; Fakhfouri et al., 2012 ) and natural CBD ( Martín-Moreno et al., 2011 ).…”