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Cited by 230Barrier Structure and Function StudiesAlzheimer's disease research and treatmentsRetinal Diseases and Treatments

Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina

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Shi, Haoshen, Koronyo, Yosef, Rentsendorj, Altan, Regis, Giovanna C., Sheyn, Julia, Fuchs, Dieu-Trang, Kramerov, Andrei A., Ljubimov, Alexander V. +8 more·2020·Acta Neuropathologica
DOI 10.1007/s00401-020-02134-wPMC PMC7181564
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Abstract

Pericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood–brain barrier breakdown described in Alzheimer’s disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of vascular-structural abnormalities and vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal vascular Aβ 40 and Aβ 42 burden. Decreased vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ 40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased vascular amyloidosis in Alzheimer’s retina implies compromised blood–retinal barrier integrity and provides new targets for AD diagnosis and therapy.

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  • Many neurodegenerative diseases are associated with loss of pericytes.

    “Many neurodegenerative diseases were found to be associated with the loss of pericytes.495,496”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [496]

    The Results section reports retinal pericyte loss and increased apoptosis in patients with mild cognitive impairment and Alzheimer’s disease. This supports an association in the Alzheimer’s disease continuum, but the paper does not establish the claim’s broader scope of many neurodegenerative diseases. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Authors
Shi, H., Koronyo, Y., Rentsendorj, A., Regis, G. C., Sheyn, J., Fuchs, D.-T., Kramerov, A. A., Ljubimov, A. V., Dumitrascu, O. M., Rodriguez, A. R., Barron, E., Hinton, D. R., Black, K. L., Miller, C. A., Mirzaei, N., & Koronyo-Hamaoui, M.
Affiliations
  • Cedars-Sinai Medical Center (US)
  • University of Southern California (US)
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2020-02-10
Volume
139
Issue
5
Pages
813-836
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-020-02134-w
PMC
PMC7181564
OpenAlex
W3005051491
Cited by
230
References
18
Citations by year
2026: 28 · 2025: 46 · 2024: 41 · 2023: 41 · 2022: 31 · 2021: 30 · 2020: 13
FWCI
11.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Institute on Aging (R01 AG055865, R01 AG056478, R01 EY13431)
  • The Maurice Marciano Family Foundation
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Keywords
Alzheimer's disease, retinal pericytes, pericyte loss, vascular amyloidosis, amyloid-beta deposition, PDGFRβ signaling, blood-retinal barrier, retinal microvasculature, LRP1, pericyte apoptosis, mild cognitive impairment, cerebral amyloid angiopathy, retinal imaging biomarkers
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Amyloidosis, Blood-Brain Barrier, Brain, Cognition, Female, Humans, Male, Retina, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Cerebral Amyloid Angiopathy, Pericytes

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