Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities

Lisa Flem Kalheim,Kjetil Vegge,Per Selnes,Tormod Fladby,Christopher Coello,Atle Bjørnerud

doi:10.3389/fneur.2016.00209

Abstract

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and cause of dementia and is characterized by amyloid plaques and neurofibrillary tangles. AD has traditionally been considered to primarily affect gray matter, but multiple lines of evidence also indicate white matter (WM) pathology and associated small-vessel cerebrovascular disease. WM glucose delivery and metabolism may have implications for local tissue integrity, and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) may be helpful to assess neuroglial and axonal function in WM. Hypothesizing that affection of oligodendroglia will be associated with loss of glucose uptake, we aimed to investigate glucose metabolism in magnetic resonance imaging (MRI) white matter hyperintensities (WMHs) and normal-appearing WM in patients with and without evidence of amyloid plaques. Subjects with mild cognitive impairment or subjective cognitive decline were included and dichotomized according to pathological (Aβ+) or normal (Aβ−) concentrations of cerebrospinal fluid amyloid-β 1–42. A total of 50 subjects were included, of whom 30 subjects were classified as Aβ(+) and 20 subjects as Aβ(−). All subjects were assessed with MRI and FDG-PET. FDG-PET images were corrected for effects of partial voluming and normalized to cerebellar WM, before determining WMH FDG-uptake. Although there were no significant differences between the groups in terms of age, WMH volume, number of individual WMHs, or WMH distribution, we found significantly lower (p = 0.021) FDG-uptake in WMHs in Aβ(+) subjects (mean = 0.662, SD = 0.113) compared to Aβ(−) subjects (mean = 0.596, SD = 0.073). There were no significant group differences in the FDG-uptake in normal-appearing WM. Similar results were obtained without correction for effects of partial voluming. Our findings add to the evidence for a link between Aβ dysmetabolism and WM pathology in AD.

Highlights

Traditionally considered two distinct entities, accumulating evidence links Alzheimer’s disease (AD) and cerebrovascular disease (CVD) [1]
The present results support an association between amyloid dysmetabolism and white matter hyperintensities (WMHs), as the lowest WMH metabolism is seen in cases with amyloid pathology
Cortical hypometabolism associated with WMHs differs from the temporoparietal pattern typically seen in AD [18, 38]

Summary

Introduction

Traditionally considered two distinct entities, accumulating evidence links Alzheimer’s disease (AD) and cerebrovascular disease (CVD) [1]. ApoEε4 alleles, a WMH Glucose Metabolism strong genetic determinant of AD risk, have been linked to both AD-related pathology (i.e., amyloid deposition) [5] and WMHs, in extensive forms and combined with vascular risk factors [6, 7]. Alzheimer’s disease is characterized by amyloid plaques and neurofibrillary tangles [9] formed by abnormal deposition of extracellular amyloid-β peptide (Aβ) and intraneuronal hyperphosphorylated tau, respectively. Low CSF Aβ shows inverse correlations with positive amyloid positron emission tomography (PET) scans [13] and amyloid plaques demonstrated at autopsy [14], probably reflecting cortical Aβ deposition

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