Skip to main content
main-content

10.02.2020 | Original Paper Open Access

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

Zeitschrift:
Acta Neuropathologica
Autoren:
Haoshen Shi, Yosef Koronyo, Altan Rentsendorj, Giovanna C. Regis, Julia Sheyn, Dieu-Trang Fuchs, Andrei A. Kramerov, Alexander V. Ljubimov, Oana M. Dumitrascu, Anthony R. Rodriguez, Ernesto Barron, David R. Hinton, Keith L. Black, Carol A. Miller, Nazanin Mirzaei, Maya Koronyo-Hamaoui
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00401-020-02134-w) contains supplementary material, which is available to authorized users.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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 Aβ40 and Aβ42 burden. Decreased vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ40 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.

Unsere Produktempfehlungen

e.Med Interdisziplinär

Kombi-Abonnement

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de. Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

Jetzt e.Med bestellen und 100 € sparen!

e.Med Neurologie & Psychiatrie

Kombi-Abonnement

Mit e.Med Neurologie & Psychiatrie erhalten Sie Zugang zu CME-Fortbildungen der Fachgebiete, den Premium-Inhalten der dazugehörigen Fachzeitschriften, inklusive einer gedruckten Zeitschrift Ihrer Wahl.

e.Med Neurologie

Kombi-Abonnement

Mit e.Med Neurologie erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes, den Premium-Inhalten der neurologischen Fachzeitschriften, inklusive einer gedruckten Neurologie-Zeitschrift Ihrer Wahl.

Zusatzmaterial
Literatur
Über diesen Artikel

Neu im Fachgebiet Pathologie

01.02.2020 | Forensische Begutachtung | CME | Ausgabe 1/2020

Diagnose einer gewaltsamen Erstickung

Teil 1: Reevaluation der Spezifität makroskopischer und histomorphologischer Befunde

27.01.2020 | Schwerpunkt: Lunge | Ausgabe 1/2020

Immunhistochemiebasierte prädiktive Biomarker bei Lungenkarzinomen

27.01.2020 | Schwerpunkt: Lunge | Ausgabe 1/2020

Zytologie der primären Lungenkarzinome