White Matter Hyperintensities are associated with Amyloid Burden in APOE4 Non-Carriers

Noh, Young; Seo, Sang Won; Jeon, Sohee; Lee, Jong Min; Kim, Jung Hyun; Kim, Geon Ha; Cho, Hanna; Yoon, Cindy W.; Kim, Hee Jin; Ye, Byoung Seok; Kim, Sung Tae; Choe, Yearn Seong; Lee, Kyung Han; Kim, Jae Seung; Ewers, Michael; Weiner, Michael W.; Lee, Jae Hong; Werring, David J.; Kang, Dae Ryong; Kim, Chang Soo; Na, Duk L.

doi:10.3233/jad-130461

Cited by 35 publications

(39 citation statements)

References 48 publications

(60 reference statements)

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“…However, the positive association between WMC and amyloid burden seemed to be predominant in the posterior brain regions, which are not the typical topography of AD but CAA. 34 Another study also reported that the volume of WMC was independently related to amyloid retention in patients with CAA but not in patients with AD. 35 On the basis of these findings, it can be speculated that WMC may be more closely linked to vascular amyloid deposition associated with CAA rather than parenchymal amyloid deposition characteristic of AD.…”

Section: Wmc and Amyloid Plaquesmentioning

confidence: 97%

“…[27][28][29]31,32 However, there were also studies showing positive relationships between WMC and amyloid. 33,34 For instance, in sporadic AD patients, WMC at baseline was significantly related to the progression of amyloid deposition in 28 months, 33 suggesting that WMC might accelerate the aggregation of amyloid protein produced in situ. However, the positive association between WMC and amyloid burden seemed to be predominant in the posterior brain regions, which are not the typical topography of AD but CAA.…”

Section: Wmc and Amyloid Plaquesmentioning

confidence: 99%

“…ПЭТ амило-ида позволяет обнаружить сопутствующее отложение амилоида у пациентов с сердечно-сосудистыми заболе-ваниями [23]. Мы рассмотрели потенциальные корре-ляции между выраженностью ЦВЗ и характеристиками амилоидных бляшек, их взаимосвязи с когнитивными нарушениями, со ссылкой на результаты in vivo клини-ческих исследований с использованием ПЭТ амилоида [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] и патологанатомических исследований с опре-делением амилоидных бляшек [41][42][43][44][45].…”

Section: Sources Of Fundingunclassified

“…В целом в большинстве исследований проде-монстрировано отсутствие корреляции между ИБВ и количеством амилоида [27-29, 31, 32]. Однако были также проведены исследования, показы-вающие наличие положительной связи между ИБВ и отложением амилоида [33,34]. Например, у пациентов со спорадической БА ИБВ исходно были значимо свя-заны с прогрессированием отложения амилоида через 28 месяцев [33], что позволяло предположить, что ИБВ могут ускорить агрегацию амилоидного белка, образуемого in situ.…”

Section: изменение белого вещества и амилоидные бляшкиunclassified

“…22 Amyloid PET can detect comorbid amyloid deposition in patients with high vascular burden. 23 We reviewed the potential interactions between CVD and amyloid plaques and their relationships with cognitive impairment, with reference to in-vivo clinical studies using amyloid PET imaging [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] and autopsy studies measuring amyloid plaques.…”

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confidence: 99%

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Cerebrovascular Disease, Amyloid Plaques, and Dementia

Liu

Wong

Law

et al. 2015

Stroke

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Absence of vascular dementia in an autopsy series from a dementia clinic. J Am Geriatr Soc. 1998;46:597-604. 6. Seno H, Ishino H, Inagaki T, Iijima M, Kaku K, Inata T. A neuropathological study of dementia in nursing homes over a 17-year period, in Shimane Prefecture, Japan. Gerontology. 1999;45:44-48. 7 However, an unresolved issue remains on the temporal relationship between the development of vascular and amyloid pathologies as other potential factors, such as the overproduction of Aβ caused by genetic mutations in APP and presenilin genes might also take part in the abnormal amyloid accumulation. Atherosclerosis and Amyloid PlaquesAtherosclerosis in large cerebral arteries can compromise cerebral blood flow and cause cerebral hypoperfusion. Patients with AD had a higher proportion and more pronounced atherosclerosis in the circle of Willis than those patients with non-AD dementias (except VaD) as shown in autopsy studies. 41,[55][56][57][58] Moreover, there was a high concordance between the ratings of atherosclerosis with amyloid plaques and CAA ratings. 41Through [18F] AV-45 PET examination, amyloid deposition in patients with dementia having unilateral carotid artery stenosis was increased. More importantly, the distribution of the amyloid disposition was found to be lateralized to the side of stenosis.26 Together, these clinical and pathological findings suggest that there is a shared cause between atherosclerosis and amyloid deposition. Infarcts and Amyloid PlaquesMost amyloid PET studies did not find significant relationships between infarcts and amyloid deposition. 27,28 In fact, a study showed that in patients with subcortical vascular cognitive impairment, the number of lacunes was negatively related with the PiB retention ratio. 29 In patients with recent ischemic stroke, although a relatively increased PiB retention was found in peri-infarct region comparing to the contralateral mirror region, this increased regional PiB retention did not translate into a higher global PiB retention. 30 In experimental stroke models in transgenic mouse with amyloid deposition (APPswe/PS1dE9), increase in new amyloid plaques around the infarcted area was only transient, in which the accumulation most probably reflected an impaired amyloid clearance pathway caused by infarcted tissue. 59 Moreover, the possibility that the observed increase in local PiB retention being a result of leakage of free PiB because of the blood-brain barrier damage could not be excluded. 30 Overall, thus far, there is no solid evidence of a significant interaction between cerebral infarcts and global amyloid burden. Sources of Funding

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Section: Wmc and Amyloid Plaquesmentioning

confidence: 97%

Section: Wmc and Amyloid Plaquesmentioning

confidence: 99%

Section: Sources Of Fundingunclassified

Section: изменение белого вещества и амилоидные бляшкиunclassified

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Cerebrovascular Disease, Amyloid Plaques, and Dementia

Liu

Wong

Law

et al. 2015

Stroke

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White matter hyperintensities influence distal cortical β‐amyloid accumulation in default mode network pathways

et al. 2023

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Background and purposeCerebral small vessel disease (SVD) has been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Yet, the role of SVD in potentially contributing to AD pathology is unclear. The main objective of this study was to test the hypothesis that WMHs influence amyloid β (Aβ) levels within connected default mode network (DMN) tracts and cortical regions in cognitively unimpaired older adults.MethodsRegional standard uptake value ratios (SUVr) from Aβ‐PET and white matter hyperintensity (WMH) volumes from three‐dimensional magnetic resonance imaging FLAIR images were analyzed across a sample of 72 clinically unimpaired (mini‐mental state examination ≥26), older adults (mean age 74.96 and standard deviation 8.13) from the Alzheimer's Disease Neuroimaging Initiative (ADNI3). The association of WMH volumes in major fiber tracts projecting from cortical DMN regions and Aβ‐PET SUVr in the connected cortical DMN regions was analyzed using linear regression models adjusted for age, sex, ApoE, and total brain volumes.ResultsThe regression analyses demonstrate that increased WMH volumes in the superior longitudinal fasciculus were associated with increased regional SUVr in the inferior parietal lobule (p = .011).ConclusionThe findings suggest that the relation between Aβ in parietal cortex is associated with SVD in downstream white matter (WM) pathways in preclinical AD. The biological relationships and interplay between Aβ and WM microstructure alterations that precede overt WMH development across the continuum of AD progression warrant further study.

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Reduced retention of Pittsburgh compound B in white matter lesions

Glodzik

Rusinek

et al. 2014

Eur J Nucl Med Mol Imaging

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Purpose One of the interesting features of amyloid tracer Pittsburgh compound B (PiB) is that it generates a signal in the white matter (WM) in both healthy subjects and cognitively impaired individuals. This characteristic gave rise to the possibility that PiB can be used to trace WM pathology. In a group of cognitively healthy elderly, we examined PiB retention in normal-appearing WM (NAWM) and white matter lesions (WML), one of the most common brain pathologies in aging. Methods We segmented WML and NAWM from fluid attenuation inversion recovery (FLAIR) images of 73 subjects (age 61.9±10.0, 71% women). PET-PiB images were corrected for partial volume effects and coregistered to FLAIR images and WM masks. WML and NAWM PiB signals were then extracted. Results PiB retention within WML was lower than in NAWM (p<.001, 14.6% reduction). This was true both for periventricular WML (p<.001, 17.8% reduction) and deep WML (p=.001, 7.5% reduction). Conclusions PiB binding in WM is influenced by the presence of WML, which lower the signal. Our findings add to the growing evidence that PiB can depict WM pathology and prompt further investigations into PiB binding targets in WM.

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White Matter Hyperintensities are associated with Amyloid Burden in APOE4 Non-Carriers

Cited by 35 publications

References 48 publications

Cerebrovascular Disease, Amyloid Plaques, and Dementia

Cerebrovascular Disease, Amyloid Plaques, and Dementia

White matter hyperintensities influence distal cortical β‐amyloid accumulation in default mode network pathways

Reduced retention of Pittsburgh compound B in white matter lesions

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