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Cerebral Amyloid Angiopathy: Emerging Evidence for Novel Pathophysiology and Pathogenesis

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Stroke Revisited: Pathophysiology of Stroke

Part of the book series: Stroke Revisited ((STROREV))

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Abstract

Cerebral amyloid angiopathy (CAA) is cerebrovascular amyloid deposition being classified into several types according to the amyloid protein involved. Of these, sporadic amyloid β-protein (Aβ)-type CAA is most commonly found in older individuals and in patients with Alzheimer’s disease (AD). Cerebral blood vessels affected with CAA are associated with functional and pathological changes (CAA-associated vasculopathies), leading to development of hemorrhagic disorders (lobar intracerebral macrohemorrhage, cortical microhemorrhage, and cortical superficial siderosis/focal convexity subarachnoid hemorrhage), ischemic disorders (white matter disease and cortical microinfarcts), and inflammatory vascular disorders, i.e., CAA-associated inflammation/angiitis; these CAA-related disorders are characterized by unique clinical features and imaging and cerebrospinal fluid abnormalities, contributing to a clinical diagnosis of CAA without brain biopsy. In this review, we particularly focus on topics with emerging evidence for novel pathophysiology and pathogenesis of CAA. They include CAA-related cognitive impairment and neurodegeneration, and CAA-related inflammation and similar disorders associated with Aβ immunotherapies for AD. Furthermore, recent studies indicated that Aβ pathologies, including CAA, would be transmissible in humans as well as experimental settings. Better understanding of mechanisms underlying pathophysiology and pathogenesis of CAA would lead to new strategies for interventions for CAA.

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Abbreviations

Aβ:

amyloid β-protein

AβPP:

β-amyloid precursor protein

ACE:

angiotensin-converting enzyme

ACT:

α1-antichymotrypsin

ACys:

amyloid cystatin C

AD:

Alzheimer’s disease

AGel:

amyloid gelsolin

AL:

amyloid immunoglobulin light chain

APOE:

apolipoprotein E

APOE:

apolipoprotein E gene

APrP:

amyloid prion protein

ARIA:

amyloid-related imaging abnormalities

ARIA-E:

amyloid-related imaging abnormalities-vasogenic edema and sulcal effusions

ARIA-H:

amyloid-related imaging abnormalities -microhemorrhages and hemosiderin deposits

ATTR:

amyloid transthyretin

BOLD:

blood-oxygen-level-dependent

CAA:

cerebral amyloid angiopathy

CAA-ri:

cerebral amyloid angiopathy-related inflammation

CBF:

cerebral blood flow

CJD:

Creutzfeldt–Jakob disease

CMB:

cerebral microbleed

cSAH:

convexity subarachnoid hemorrhage

CSF:

cerebrospinal fluid

cSS:

cortical superficial siderosis

dCJD:

dura mater graft-associated Creutzfeldt–Jakob disease

DMT:

disease-modifying therapies

FDG:

fluorodeoxyglucose

FLAIR:

fluid attenuation inversion recovery

fMRI:

functional MRI

hGH:

human cadaveric pituitary-derived growth hormone

ICH:

intracerebral hemorrhage

iCJD:

iatrogenic CJD

LRP-1:

low-density lipoprotein-receptor related protein

MB:

microbleed

MCI:

mild cognitive impairment

PiB:

Pittsburgh Compound B

PS1:

presenilin 1

p-tau:

phosphorylated tau

p-TDP-43:

phosphorylated transactive response DNA binding protein 43 kDa

SAH:

subarachnoid hemorrhage

sCJD:

sporadic Creutzfeldt-Jakob disease

SVD:

small vessel disease

TDP-43:

transactive response DNA binding protein 43 kDa

TGF-β1:

Another CAA-related gene reported by more than one research group transforming growth factor-β1

VaD:

vascular dementia

WMH:

white matter hyperintensity

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Authors and Affiliations

  1. Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan

    Masahito Yamada, Kenji Sakai, Tsuyoshi Hamaguchi & Moeko Noguchi-Shinohara

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  1. Masahito Yamada
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  2. Kenji Sakai
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  3. Tsuyoshi Hamaguchi
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  4. Moeko Noguchi-Shinohara
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Correspondence to Masahito Yamada .

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Editors and Affiliations

  1. Department of Neurology, Seoul National University Hospital, Seoul, Korea (Republic of)

    Seung-Hoon Lee

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Yamada, M., Sakai, K., Hamaguchi, T., Noguchi-Shinohara, M. (2020). Cerebral Amyloid Angiopathy: Emerging Evidence for Novel Pathophysiology and Pathogenesis. In: Lee, SH. (eds) Stroke Revisited: Pathophysiology of Stroke. Stroke Revisited. Springer, Singapore. https://doi.org/10.1007/978-981-10-1430-7_7

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  • DOI: https://doi.org/10.1007/978-981-10-1430-7_7

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