P4-259: White matter hyperintensities in Alzheimer's disease: The potential protective role of vitamin D

Abstract Background White matter hyperintensities (WMH) are frequently found in Alzheimer’s disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with Aβ burden, glucose hypometabolism, and gray matter volume reduction. Methods In a total of 155 participants (IMAP+ cohort) across the cognitive continuum from normal cognition to AD dementia, FLAIR MRI, AV45-PET, FDG-PET, and T1 MRI were acquired. WMH were automatically segmented from FLAIR images. Mean levels of neocortical Aβ deposition (AV45-PET), temporo-parietal glucose metabolism (FDG-PET), and medial-temporal gray matter volume (GMV) were extracted from processed images using established AD meta-signature templates. Associations between AD brain biomarkers and WMH, as assessed in region-of-interest and voxel-wise, were examined, adjusting for age, sex, education, and systolic blood pressure. Results There were no significant associations between global Aβ burden and region-specific WMH. Voxel-wise WMH in the splenium of the corpus callosum correlated with greater Aβ deposition at a more liberal threshold. Region- and voxel-based WMH in the posterior corpus callosum, along with parietal, occipital, and frontal areas, were associated with lower temporo-parietal glucose metabolism. Similarly, lower medial-temporal GMV correlated with WMH in the posterior corpus callosum in addition to parietal, occipital, and fontal areas. Conclusions This study demonstrates that local white matter damage is correlated with multimodal brain biomarkers of AD. Our results highlight modality-specific topographic patterns of WMH, which converged in the posterior white matter. Overall, these cross-sectional findings corroborate associations of regional WMH with AD-typical Aß deposition and neurodegeneration.

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P1-345: Role of Vitamin D Signaling in Sporadic Alzheimer’s Disease: A Clinico-Experimental Study

Alzheimer s & Dementia ◽

10.1016/j.jalz.2016.06.1096 ◽

2016 ◽

Vol 12 ◽

pp. P561-P562

Author(s):

Anindita Banerjee ◽

Vineet Kumar Khemka ◽

Debashree Roy ◽

Aparajita Dhar ◽

Tapan Kumar Sinha Roy ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Experimental Study ◽

Vitamin D ◽

Sporadic Alzheimer’S Disease ◽

Vitamin D Signaling

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Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

Journal of Alzheimer s Disease ◽

10.3233/jad-210333 ◽

2021 ◽

pp. 1-11

Author(s):

Fennie Choy Chin Wong ◽

Seyed Ehsan Saffari ◽

Chathuri Yatawara ◽

Kok Pin Ng ◽

Nagaendran Kandiah ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Executive Function ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Amyloid Β ◽

Intracranial Volume ◽

Linear Regression Models ◽

Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

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Regional white matter hyperintensities: aging, Alzheimer's disease risk, and cognitive function

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2013.10.072 ◽

2014 ◽

Vol 35 (4) ◽

pp. 769-776 ◽

Cited By ~ 59

Author(s):

Alex C. Birdsill ◽

Rebecca L. Koscik ◽

Erin M. Jonaitis ◽

Sterling C. Johnson ◽

Ozioma C. Okonkwo ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Function ◽

White Matter ◽

White Matter Hyperintensities ◽

Disease Risk

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White matter hyperintensities and changes in white matter integrity in patients with Alzheimer’s disease

Neuroradiology ◽

10.1007/s00234-010-0806-2 ◽

2010 ◽

Vol 53 (5) ◽

pp. 373-381 ◽

Cited By ~ 16

Author(s):

Liya Wang ◽

Felicia C. Goldstein ◽

Allan I. Levey ◽

James J. Lah ◽

Carolyn C. Meltzer ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

White Matter Hyperintensities ◽

White Matter Integrity

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Dynamic Progression of White Matter Hyperintensities in Alzheimer’s Disease and Normal Aging: Results from the Sunnybrook Dementia Study

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2016.00062 ◽

2016 ◽

Vol 8 ◽

Cited By ~ 17

Author(s):

Joel Ramirez ◽

Alicia A. McNeely ◽

Courtney Berezuk ◽

Fuqiang Gao ◽

Sandra E. Black

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

White Matter Hyperintensities ◽

Normal Aging

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Genetic Variants of Lipoprotein Lipase and Regulatory Factors Associated with Alzheimer’s Disease Risk

International Journal of Molecular Sciences ◽

10.3390/ijms21218338 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8338

Author(s):

Kimberley D. Bruce ◽

Maoping Tang ◽

Philip Reigan ◽

Robert H. Eckel

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Lipoprotein Lipase ◽

Genetic Variants ◽

Disease Risk ◽

Lipoprotein Metabolism ◽

Protective Role ◽

Direct Role ◽

The Brain

Lipoprotein lipase (LPL) is a key enzyme in lipid and lipoprotein metabolism. The canonical role of LPL involves the hydrolysis of triglyceride-rich lipoproteins for the provision of FFAs to metabolic tissues. However, LPL may also contribute to lipoprotein uptake by acting as a molecular bridge between lipoproteins and cell surface receptors. Recent studies have shown that LPL is abundantly expressed in the brain and predominantly expressed in the macrophages and microglia of the human and murine brain. Moreover, recent findings suggest that LPL plays a direct role in microglial function, metabolism, and phagocytosis of extracellular factors such as amyloid- beta (Aβ). Although the precise function of LPL in the brain remains to be determined, several studies have implicated LPL variants in Alzheimer’s disease (AD) risk. For example, while mutations shown to have a deleterious effect on LPL function and expression (e.g., N291S, HindIII, and PvuII) have been associated with increased AD risk, a mutation associated with increased bridging function (S447X) may be protective against AD. Recent studies have also shown that genetic variants in endogenous LPL activators (ApoC-II) and inhibitors (ApoC-III) can increase and decrease AD risk, respectively, consistent with the notion that LPL may play a protective role in AD pathogenesis. Here, we review recent advances in our understanding of LPL structure and function, which largely point to a protective role of functional LPL in AD neuropathogenesis.

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