Cortical angiopathy in Alzheimer's disease: The formation of dystrophic perivascular neurites is related to the exudation of amyloid fibrils from the pathological vessels

Peers, Marie-Claire; Lenders, Marie-Berthe; Défossez, A.; Delacourte, A.; Mazzuca, M

doi:10.1007/bf00749733

Cited by 21 publications

(8 citation statements)

References 18 publications

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“…Present observations extend previous anecdotal reports of abnormal accumulation of tau in dystrophic neurites around cortical blood vessels with dyshoric amyloid angiopathy [6–8,12]. The fact that tau also tends to accumulate around blood vessels with little or no amyloid indicates that the relationship is not simply a manifestation of a direct interaction between amyloid and adjacent neurites.…”

Section: Discussionsupporting

confidence: 89%

Relationship of neurofibrillary pathology to cerebral amyloid angiopathy in Alzheimer's disease

Williams¹,

Chalmers²,

Wilcock³

et al. 2005

Neuropathology Appl Neurobio

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Over 90% of patients with Alzheimer's disease (AD) develop cerebral amyloid angiopathy (CAA). Severe dyshoric CAA, in which amyloid extends into the surrounding brain parenchyma, may be associated with adjacent clustering of tau-immunopositive neurites but the relationship of CAA to neurofibrillary pathology has not been systematically investigated. In the present study this relationship was examined in sections of frontal, temporal and parietal cortex from 25 AD patients with moderate to severe CAA and 26 with mild or absent CAA. We measured immunolabelling of abnormally phosphorylated tau adjacent to A beta-laden and non-A beta-laden arteries and arterioles, and in cortex away from arteries and arterioles. We also analysed the possible influence of APOE genotype on these measurements. There were no significant differences between the lobes in measurements of tau labelling, either around blood vessels or elsewhere in the cortex. However, tau labelling around A beta-laden arteries and arterioles significantly exceeded that around non-A beta-laden blood vessels (P<0.001) and this, in turn was greater than the labelling of cortex away from blood vessels (P<0.001). There was no association between APOE epsilon 4 and the immunolabelling density for tau, whether around amyloid- or non-amyloid-laden arteries and arterioles, or in the cerebral cortex away from these. We propose that both CAA and peri-vascular accumulation of hyperphosphorylated tau may be a consequence of elevated levels of soluble A beta around cortical arteries and arterioles.

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Section: Discussionsupporting

confidence: 89%

Relationship of neurofibrillary pathology to cerebral amyloid angiopathy in Alzheimer's disease

Williams¹,

Chalmers²,

Wilcock³

et al. 2005

Neuropathology Appl Neurobio

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“…However, the excreted Aβ than consists mainly of Aβ 40 , which is hypothesized to travel further than the plaque-associated Aβ 42 due to increased solubility and only aggregates once it reaches the (peri)vasculair drainage system [22]. The complement cascade becomes also activated and dystrophic neurites can be found surrounding the congophilic vessels [37,38,56]. However, different from plaques, microglial and macrophage activity markers in CAA do not seem to be increased compared to control vessels [56].…”

Section: Discussionmentioning

confidence: 99%

The coarse-grained plaque: a divergent Aβ plaque-type in early-onset Alzheimer’s disease

et al. 2020

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Alzheimer’s disease (AD) is characterized by amyloid-beta (Aβ) deposits, which come in myriad morphologies with varying clinical relevance. Previously, we observed an atypical Aβ deposit, referred to as the coarse-grained plaque. In this study, we evaluate the plaque’s association with clinical disease and perform in-depth immunohistochemical and morphological characterization. The coarse-grained plaque, a relatively large (Ø ≈ 80 µm) deposit, characterized as having multiple cores and Aβ-devoid pores, was prominent in the neocortex. The plaque was semi-quantitatively scored in the middle frontal gyrus of Aβ-positive cases (n = 74), including non-demented cases (n = 15), early-onset (EO)AD (n = 38), and late-onset (LO)AD cases (n = 21). The coarse-grained plaque was only observed in cases with clinical dementia and more frequently present in EOAD compared to LOAD. This plaque was associated with a homozygous APOE ε4 status and cerebral amyloid angiopathy (CAA). In-depth characterization was done by studying the coarse-grained plaque’s neuritic component (pTau, APP, PrPC), Aβ isoform composition (Aβ40, Aβ42, AβN3pE, pSer8Aβ), its neuroinflammatory component (C4b, CD68, MHC-II, GFAP), and its vascular attribution (laminin, collagen IV, norrin). The plaque was compared to the classic cored plaque, cotton wool plaque, and CAA. Similar to CAA but different from classic cored plaques, the coarse-grained plaque was predominantly composed of Aβ40. Furthermore, the coarse-grained plaque was distinctly associated with both intense neuroinflammation and vascular (capillary) pathology. Confocal laser scanning microscopy (CLSM) and 3D analysis revealed for most coarse-grained plaques a particular Aβ40 shell structure and a direct relation with vessels. Based on its morphological and biochemical characteristics, we conclude that the coarse-grained plaque is a divergent Aβ plaque-type associated with EOAD. Differences in Aβ processing and aggregation, neuroinflammatory response, and vascular clearance may presumably underlie the difference between coarse-grained plaques and other Aβ deposits. Disentangling specific Aβ deposits between AD subgroups may be important in the search for disease-mechanistic-based therapies.

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“…The limbic structures also show severe neurofibrillary pathology, and as in FBD, ANs are restricted to areas with amyloid deposition and are therefore largely associated with CAA. In addition to the BRI2 gene-related conditions, perivascular clustering of argyrophilic and tauimmunoreactive abnormal neurites can also occur in relation to A␤ (93,118) and prion protein-related CAAs (26). Another difference between FDD and FBD is that in the former the neocortex is more affected by both pre-amyloid peptide deposition and neurofibrillary pathology than in FBD.…”

Section: Hereditary Caas Hchwa-d and Familial Admentioning

confidence: 99%

Sporadic and Familial Cerebral Amyloid Angiopathies

et al. 2002

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Cerebral amyloid angiopathy (CAA) is the term used to describe deposition of amyloid in the walls of arteries, arterioles and, less often, capillaries and veins of the central nervous system. CAAs are an important cause of cerebral hemorrhage and may also result in ischemic lesions and dementia. A number of amyloid proteins are known to cause CAA. The most common sporadic CAA, caused by Aβ deposition, is associated with aging and is a common feature of Alzheimer disease (AD). CAA occurs in several familial conditions, including hereditary cerebral hemorrhage with amyloidosis of Icelandic type caused by deposition of mutant cystatin C, hereditary cerebral hemorrhage with amyloidosis Dutch type and familial AD with deposition of either Aβ variants or wild‐type Aβ, the transthyretin‐related meningo‐vascular amyloidoses, gelsolin as well as familial prion disease‐related CAAs and the recently described BRI2 gene‐related CAAs in familial British dementia and familial Danish dementia. This review focuses on the morphological, biochemical, and genetic aspects as well as the clinical significance of CAAs with special emphasis on the BRI2 gene‐related cerebrovascular amyloidoses. We also discuss data relevant to the pathomechanism of the different forms of CAA with an emphasis on the most common Aβ‐related types.

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Cortical angiopathy in Alzheimer's disease: The formation of dystrophic perivascular neurites is related to the exudation of amyloid fibrils from the pathological vessels

Cited by 21 publications

References 18 publications

Relationship of neurofibrillary pathology to cerebral amyloid angiopathy in Alzheimer's disease

Relationship of neurofibrillary pathology to cerebral amyloid angiopathy in Alzheimer's disease

The coarse-grained plaque: a divergent Aβ plaque-type in early-onset Alzheimer’s disease

Sporadic and Familial Cerebral Amyloid Angiopathies

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