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Venular amyloid and its relationship with cerebral amyloid angiopathy in TGF344AD rats
Author(s) -
Bishay Jossana,
Beckett Tina,
Lai Aaron Y.,
Hill Mary E.,
McMahon Dallan,
Simpson Craig,
Hynynen Kullervo,
McLaurin JoAnne
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.042458
Subject(s) - cerebral amyloid angiopathy , pathology , thioflavin , amyloid (mycology) , parenchyma , laser capture microdissection , alzheimer's disease , senile plaques , perivascular space , amyloidosis , angiopathy , biology , medicine , dementia , disease , endocrinology , biochemistry , gene expression , gene , diabetes mellitus
Background In Alzheimer’s Disease (AD), the amyloid‐beta peptide (Aβ) aggregates and deposits in the form of amyloid plaques within the brain parenchyma. Overproduction of Aβ is less common in sporadic AD cases, suggesting that impairment in Aβ clearance contributes to disease pathology. In AD, failure of the perivascular drainage pathway leads to Aβ deposition in the walls of cerebral blood vessels, resulting in cerebral amyloid angiopathy (CAA). The association between amyloid deposits with arterioles and capillaries is known, however, amyloid deposits present in venules is still controversial. Method A TgF344‐AD rat model overexpressing the human APPswe and PS1ΔE9 mutations was used as it recapitulates the typical hallmarks of AD in humans, including Aβ plaque formation, CAA, tau pathology, frank neuronal loss, and cognitive deficits. At 7, 10, 13, and 16 months of age, brain sections were examined by immunofluorescence staining and image analyses for amyloid deposits around all blood vessels using Thioflavin S staining. Further identification of deposits with Aβ specific antibodies, 4G8 (17‐28), MOAB2 (1‐4), and anti‐Aβ1‐40/42, were used to confirm Thioflavin results. Amyloid aggregates were isolated from parenchymal plaques, CAA, and venular amyloid using a laser capture microdissection (LCM) microscope and sent for mass‐spectrometry (MS) to identify the presence of Aβ. Result Results suggest as an increase in CAA is detected, venular amyloid starts to accumulate, with disease progression. Confirmation with antibodies that span the Aβ sequence, 4G8, MOAB2, anti‐Aβ1‐40/42, identify amyloid deposits in both venules and arterioles. Furthermore, LCM‐MS technique identified presence of Aβ in cortical plaques and CAA samples. Conclusion Correlation with venular amyloid deposition and CAA suggests an important interplay between these vascular pathologies with AD progression. Understanding venular amyloid and its relationship with CAA can play a role in studying mechanisms involved in neurovascular dysfunction of AD.