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Review
. 2018 Oct;13(10):1719-1730.
doi: 10.4103/1673-5374.238608.

Distinguishing normal brain aging from the development of Alzheimer's disease: inflammation, insulin signaling and cognition

Paul Denver  1 , Paula L McClean  2
Affiliations
Review

Distinguishing normal brain aging from the development of Alzheimer's disease: inflammation, insulin signaling and cognition

Paul Denver et al. Neural Regen Res. 2018 Oct.

Abstract

As populations age, prevalence of Alzheimer's disease (AD) is rising. Over 100 years of research has provided valuable insights into the pathophysiology of the disease, for which age is the principal risk factor. However, in recent years, a multitude of clinical trial failures has led to pharmaceutical corporations becoming more and more unwilling to support drug development in AD. It is possible that dependence on the amyloid cascade hypothesis as a guide for preclinical research and drug discovery is part of the problem. Accumulating evidence suggests that amyloid plaques and tau tangles are evident in non-demented individuals and that reducing or clearing these lesions does not always result in clinical improvement. Normal aging is associated with pathologies and cognitive decline that are similar to those observed in AD, making differentiation of AD-related cognitive decline and neuropathology challenging. In this mini-review, we discuss the difficulties with discerning normal, age-related cognitive decline with that related to AD. We also discuss some neuropathological features of AD and aging, including amyloid and tau pathology, synapse loss, inflammation and insulin signaling in the brain, with a view to highlighting cognitive or neuropathological markers that distinguish AD from normal aging. It is hoped that this review will help to bolster future preclinical research and support the development of clinical tools and therapeutics for AD.

Keywords: Alzheimer's disease; aging; cognitive function; cytokines; inflammation; insulin signaling; spatial learning; synapses.

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Conflict of interest statement

Some of the data from Denver et al. (2018) has been submitted, in abstract form, to the 2017 Southern California Alzheimer's Disease Centers Research Symposium at the University of California, Beckman Center of the National Academies of Sciences & Engineering, Irvine, CA, USA

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