Amyloid, tau, pathogen infection and antimicrobial protection in Alzheimer’s disease –conformist, nonconformist, and realistic prospects for AD pathogenesis
Year: 2018
Type: review
Abstract: BACKGROUND: Alzheimer's disease (AD) is a fatal disease that threatens the quality of life of an aging population at a global scale. Various hypotheses on the etiology of AD have been developed over the years to guide efforts in search of therapeutic strategies. MAIN BODY: In this review, we focus on four AD hypotheses currently relevant to AD onset: the prevailing amyloid cascade hypothesis, the well-recognized tau hypothesis, the increasingly popular pathogen (viral infection) hypothesis, and the infection-related antimicrobial protection hypothesis. In briefly reviewing the main evidence supporting each hypothesis and discussing the questions that need to be addressed, we hope to gain a better understanding of the complicated multi-layered interactions in potential causal and/or risk factors in AD pathogenesis. As a defining feature of AD, the existence of amyloid deposits is likely fundamental to AD onset but is insufficient to wholly reproduce many complexities of the disorder. A similar belief is currently also applied to hyperphosphorylated tau aggregates within neurons, where tau has been postulated to drive neurodegeneration in the presence of pre-existing Aβ plaques in the brain. Although infection of the central nerve system by pathogens such as viruses may increase AD risk, it is yet to be determined whether this phenomenon is applicable to all cases of sporadic AD and whether it is a primary trigger for AD onset. Lastly, the antimicrobial protection hypothesis provides insight into a potential physiological role for Aβ peptides, but how Aβ/microbial interactions affect AD pathogenesis during aging awaits further validation. Nevertheless, this hypothesis cautions potential adverse effects in Aβ-targeting therapies by hindering potential roles for Aβ in anti-viral protection. CONCLUSION: AD is a multi-factor complex disorder, which likely requires a combinatorial therapeutic approach to successfully slow or reduce symptomatic memory decline. A better understanding of how various causal and/or risk factors affecting disease onset and progression will enhance the likelihood of conceiving effective treatment paradigms, which may involve personalized treatment strategies for individual patients at varying stages of disease progression.
Source: Translational Neurodegeneration
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,990
Awards: Pathogenic effects of plasma ApoE on CNS function and Alzheimer's disease, Effects of peripheral apoE isoforms on inflammation, brain vasculature, and AD pathogenesis, G2564371383, The role of neuronal HSPG in the propagation of Tau, Novel roles for the Alzheimer's Disease (AD) risk gene, SORLA in neuroprotection in AD, Convergence of tauopathy and Huntington's disease through selective autophagy, Decoding the role of diverse astrocyte populations in aging and AD, Knockin mouse models of Alzheimer's Disease, A role for TREM2/Abeta interactions in microglia-regulated AD pathogenesis, Targeting a lipid-mediated pro-longevity pathway as Alzheimer's therapy, G9000302932, Knockin mouse models of Alzheimer's Disease
OpenAlex ID: W2906630689