Cited by 117Alzheimer's disease research and treatmentsNeurological Disease Mechanisms and TreatmentsDementia and Cognitive Impairment Research

Chronic cerebral hypoperfusion enhances Tau hyperphosphorylation and reduces autophagy in Alzheimer’s disease mice

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Qiu, Lifeng, Ng, Gandi, Tan, Eng King, Liao, Ping, Kandiah, Nagaendran, Zeng, Li·2016·Scientific Reports

Abstract

Cerebral hypoperfusion and impaired autophagy are two etiological factors that have been identified as being associated with the development of Alzheimer’s disease (AD). Nevertheless, the exact relationships among these pathological processes remain unknown. To elucidate the impact of cerebral hypoperfusion in AD, we created a unilateral common carotid artery occlusion (UCCAO) model by occluding the left common carotid artery in both young and old 3xTg-AD mice. Two months after occlusion, we found that ligation increases phospho-Tau (p-Tau) at Serine 199/202 in the hippocampus of 3-month-old AD mice, compared to sham-operated AD mice; whereas, there is no change in the wild type (WT) mice after ligation. Moreover, cerebral hypoperfusion led to significant increase of p-Tau in both the hippocampus and cortex of 16-month-old AD mice and WT mice. Notably, we did not detect any change in Aβ 42 level in either young or old AD and WT mice after ligation. Interestingly, we observed a downregulation of LC3-II in the cortex of aged AD mice and WT mice after ligation. Our results suggest that elevated p-Tau and reduced autophagy are major cellular changes that are associated with hypoperfusion in AD. Therefore, targeting p-Tau and autophagy pathways may ameliorate hypoperfusion-induced brain damage in AD.

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Authors
Qiu, L., Ng, G., Tan, E. K., Liao, P., Kandiah, N., & Zeng, L.
Affiliations
  • National Neuroscience Institute (SG)
  • Singapore General Hospital (SG)
  • Duke-NUS Medical School (SG)
Corresponding author
  • Liao, Ping
  • Kandiah, Nagaendran
  • Zeng, Li
Venue
Scientific Reports
Published
2016-04-06
Volume
6
Issue
1
Pages
23964-23964
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2317915347
Cited by
115
References
49
Citations by year
2026: 6 · 2025: 12 · 2024: 10 · 2023: 13 · 2022: 9 · 2021: 14 · 2020: 17 · 2019: 11 · 2018: 18 · 2017: 4 · 2016: 1
FWCI
9.13
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion)
Funders
  • National Research Foundation
  • National Research Foundation Singapore
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, cerebral hypoperfusion, tau hyperphosphorylation, autophagy, 3xTg-AD mice, common carotid artery occlusion, hippocampus, LC3-II, amyloid-beta 42, aging, cerebral ischemia
MeSH terms
Age Factors, Alzheimer Disease, Animals, Autophagy, Brain Ischemia, Chronic Disease, Disease Models, Animal, Female, Frontal Lobe, Hippocampus, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Microtubule-Associated Proteins, Peptide Fragments, Phosphorylation, Immunoblotting, Amyloid beta-Peptides, tau Proteins, Mice, 129 Strain

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