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Amyloid-β in Brain Aging and Alzheimer’s Disease

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Aging Mechanisms II

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Abstract

During aging, the brain milieu changes in a multitude of ways, resulting in a decline of physiological functions and increased susceptibility to disease. One of the major age-related pathological changes in the brain is the accumulation of amyloid-β (Aβ) peptides as plaques. The appearance of pathologic Aβ species is believed to trigger Alzheimer’s disease (AD), one of the principal neurodegenerative diseases and the leading cause of dementia, of which aging is the most important risk factor. Accumulation of Aβ in the brain is caused by an imbalance in Aβ kinetics that may arise from aging-related changes in degradation or clearance mechanisms. Aβ is degraded by enzymes such as neprilysin and is removed from the brain via numerous pathways including glial phagocytosis, transport across the blood-brain barrier, interstitial fluid bulk flow, and cerebrospinal fluid absorption. The functional activity of many of these systems declines with aging. Elevated levels of pathogenic Aβ species result in the emergence of senile plaques in the neuropil or as cerebral amyloid angiopathy in blood vessels. In addition, soluble Aβ oligomers appear prior to amyloid fibril formation and have detrimental effects on neuronal functions. To elucidate the pathomechanisms underlying AD, we have previously developed new mouse models that precisely recapitulate amyloid pathology without overexpressing disease-relevant molecules. Here we provide an overview of the catabolism, anabolism, and clearance of Aβ, the characteristics of amyloid pathologies in the human brain, and recent advances in AD research, including new technologies and animal models.

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  1. Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan

    Hiroki Sasaguri & Takaomi C. Saido

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  1. Hiroki Sasaguri
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  1. Fukuoka International University of Health and Welfare, Fukuoka, Japan

    Nozomu Mori

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Sasaguri, H., Saido, T.C. (2022). Amyloid-β in Brain Aging and Alzheimer’s Disease. In: Mori, N. (eds) Aging Mechanisms II . Springer, Singapore. https://doi.org/10.1007/978-981-16-7977-3_21

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