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From Chronic Cerebral Hypoperfusion to Alzheimer-Like Brain Pathology and Neurodegeneration

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Abstract

Chronic cerebral hypoperfusion (CCH) is a common consequence of various cerebral vascular disorders and hemodynamic and blood changes. Recent studies have revealed an important role of CCH in neurodegeneration and dementia, including vascular dementia and Alzheimer’s disease (AD). This article reviews the recent advances in understanding CCH-induced neurodegeneration and AD-related brain pathology and cognitive impairment. We discuss the causes and assessment of CCH, the possible mechanisms by which CCH promotes Alzheimer-like pathology and neurodegeneration, and animal models of CCH. It appears that CCH promotes neurodegeneration and AD through multiple mechanisms, including induction of oxidative stress, Aβ accumulation and aggravation, tau hyperphosphorylation, synaptic dysfunction, neuronal loss, white matter lesion, and neuroinflammation. Better understanding of the mechanisms of CCH will help develop therapeutic strategies for preventing and treating neurodegeneration, including sporadic AD and vascular dementia, caused by CCH.

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Abbreviations

AD:

Alzheimer’s disease

APP:

Amyloid β precursor protein

ASK1:

Apoptosis signal-regulating kinase 1

BCAS:

Bilateral common carotid artery stenosis

BCCAO:

Bilateral common carotid artery occlusion

CaMK-II:

Calcium/calmodulin-dependent protein kinase II

CCH:

Chronic cerebral hypoperfusion

CDK5:

Cyclin dependent kinases 5

ERK1/2:

Extracellular signal-regulated kinases

GLUTs:

Glucose transporters

GSK-3β:

Glycogen synthase kinase-3β

HIF-1:

Hypoxia inducible factor-1

IL-1β:

Interleukin-1β

JNK:

c-Jun N-terminal kinase

LTP:

Long-term potentiation

MAPK:

Mitogen-activated protein kinase

NFTs:

Neurofibrillary tangles

PP2A:

Protein phosphatase 2A

PSD95:

Postsynaptic density protein 95

TIGAR:

TP53-induced glycolysis and apoptosis regulator

UCCAO:

Unilateral common carotid artery occlusion

VaD:

Vascular dementia

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Acknowledgments

Studies performed in the authors’ laboratory were supported in part by the New York State Office for People with Developmental Disabilities. We thank Ms. M. Marlow of the New York State Institute for Basic Research in Developmental Disabilities for her editorial assistance.

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The authors declare that they have no conflict of interest.

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Correspondence to Cheng-Xin Gong.

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Zhao, Y., Gong, CX. From Chronic Cerebral Hypoperfusion to Alzheimer-Like Brain Pathology and Neurodegeneration. Cell Mol Neurobiol 35, 101–110 (2015). https://doi.org/10.1007/s10571-014-0127-9

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  • DOI: https://doi.org/10.1007/s10571-014-0127-9

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