Distinct White Matter Changes Associated with Cerebrospinal Fluid Amyloid-β1-42 and Hypertension

Al‐Janabi, Omar; Brown, Christopher; Bahrani, Ahmed A.; Abner, Erin L.; Barber, Justin M.; Gold, Brian T.; Goldstein, Larry B.; Murphy, Richard R.; Nelson, Peter T.; Johnson, Nancy E.; Shaw, Leslie M.; Smith, Charles D.; Trojanowski, John Q.; Wilcock, Donna M.; Jicha, Gregory A.

doi:10.3233/jad-180663

Cited by 22 publications

(22 citation statements)

References 53 publications

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“…Chronic ischemia alters mechanisms of perivascular lymphatic drainage of interstitial fluid, leading to the accumulation of amyloid and further exacerbating the hypoxic environment (Huang et al, 2010). More recent evidence from a smaller cognitively mixed study suggests that greater CSF Aβ 1–42 is associated with lower WMH burden (Al-Janabi et al, 2018). Similar trends have been observed in amyloid PET imaging studies (Goodheart et al, 2015), though this may differ by APOE ε4 allele status (Noh et al, 2014).…”

Section: White Matter Hyperintensities Of Presumed Vascular Originmentioning

confidence: 99%

Neuroimaging of Cerebral Small Vessel Disease and Age-Related Cognitive Changes

Caunca

León-Benedetti

Latour

et al. 2019

Front. Aging Neurosci.

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Subclinical cerebrovascular disease is frequently identified in neuroimaging studies and is thought to play a role in the pathogenesis of cognitive disorders. Identifying the etiologies of different types of lesions may help investigators differentiate between age-related and pathological cerebrovascular damage in cognitive aging. In this review article, we aim to describe the epidemiology and etiology of various brain magnetic resonance imaging (MRI) measures of vascular damage in cognitively normal, older adult populations. We focus here on population-based prospective cohort studies of cognitively unimpaired older adults, as well as discuss the heterogeneity of MRI findings and their relationships with cognition. This review article emphasizes the need for a better understanding of subclinical cerebrovascular disease in cognitively normal populations, in order to more effectively identify and prevent cognitive decline in our rapidly aging population.

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Section: White Matter Hyperintensities Of Presumed Vascular Originmentioning

confidence: 99%

Neuroimaging of Cerebral Small Vessel Disease and Age-Related Cognitive Changes

Caunca

León-Benedetti

Latour

et al. 2019

Front. Aging Neurosci.

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“…Structural magnetic resonance imaging (MRI) is the most widely used and standardized method for cSVD diagnoses and research applications, owing both to its high spatial resolution and its ability to detect a spectrum of cerebrovascular abnormalities without the need for application of extensive post-acquisition image analyses. There is currently no universally accepted method for categorizing cerebral cSVD using MRI but proposed standards are evolving as the main, but not the only underlying cause of WMH [7,210].…”

Section: Neuroimagingmentioning

confidence: 99%

Brain arteriolosclerosis

et al. 2020

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Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as A a a b c-predominant age-related TDP-43 encephalopathy (LATE).There may also be complex physiologic interactions between metabolic syndrome (e.g. hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that include consideration of comorbid diseases, B-ASC is independently associated with impairments in global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability.

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“…Participants at UCSF and UKy were scanned with the same type of Siemens Prisma 3Tsystem and images were analyzed by the methods described . All images at both UCSF and UKy were rated for burden of WMH by a board‐certified neurologist in addition to being reviewed by a neuroradiologist to rule out other significant abnormalities.…”

Section: Methodsmentioning

confidence: 99%

Endothelial‐derived plasma exosome proteins in Alzheimer’s disease angiopathy

et al. 2020

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Small cerebral vascular disease (SCeVD) demonstrated by white matter hyperintensity (WMH) on MRI contributes to the development of dementia in Alzheimer's disease (AD), but it has not been possible to correlate onset, severity, or protein components of SCeVD with characteristics of WMH in living patients. Plasma endothelial‐derived exosomes (EDEs) were enriched by two‐step immunoabsorption from four groups of participants with no clinical evidence of cerebrovascular disease: cognitively normal (CN) without WMH (CN without SCeVD, n = 20), CN with SCeVD (n = 22), preclinical AD (pAD) + mild cognitive impairment (MCI) without SCeVD (pAD/MCI without SCeVD, n = 22), and pAD/MCI with SCeVD (n = 16) for ELISA quantification of cargo proteins. Exosome marker CD81‐normalized EDE levels of the cerebrovascular‐selective biomarkers large neutral amino acid transporter 1 (LAT‐1), glucose transporter type 1 (Glut‐1), and permeability‐glycoprotein (p‐GP, ABCB1) were similarly significantly higher in the CN with SCeVD and pAD/MCI with SCeVD groups than their corresponding control groups without SCeVD. CD81‐normalized EDE levels of Aβ40 and Aβ42 were significantly higher in the pAD/MCI with SCeVD group but not in the CN with SCeVD group relative to controls without SCeVD. Levels of normal cellular prion protein (PrPc), a receptor for amyloid peptides, and phospho‐181T‐tau were higher in both CN and pAD/MCI with SCeVD groups than in the corresponding controls. High EDE levels of Aβ40, Aβ42, and phospho‐181T‐tau in patients with WMH suggesting SCeVD appear at the pre‐clinical or MCI stage of AD and therapeutic lowering of neurotoxic peptide levels may delay progression of AD angiopathy.

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Distinct White Matter Changes Associated with Cerebrospinal Fluid Amyloid-β1-42 and Hypertension

Cited by 22 publications

References 53 publications

Neuroimaging of Cerebral Small Vessel Disease and Age-Related Cognitive Changes

Neuroimaging of Cerebral Small Vessel Disease and Age-Related Cognitive Changes

Brain arteriolosclerosis

Endothelial‐derived plasma exosome proteins in Alzheimer’s disease angiopathy

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