Abstract
AimsMost individuals with AD neuropathological changes have co‐morbidities which have an impact on the integrity of the WM. This study analyses oligodendrocyte and myelin markers in the frontal WM in a series of AD cases without clinical or pathological co‐morbidities.MethodsFrom a consecutive autopsy series, 206 cases had neuropathological changes of AD; among them, only 33 were AD without co‐morbidities. WM alterations were first evaluated in coronal sections of the frontal lobe in every case. Then, RT‐qPCR and immunohistochemistry were carried out in the frontal WM of AD cases without co‐morbidities to analyse the expression of selected oligodendrocyte and myelin markers.ResultsWM demyelination was more marked in AD with co‐morbidities when compared with AD cases without co‐morbidities. Regarding the later, mRNA expression levels of MBP, PLP1, CNP, MAG, MAL, MOG and MOBP were preserved at stages I–II/0–A when compared with middle‐aged (MA) individuals, but significantly decreased at stages III–IV/0–C. This was accompanied by reduced expression of NG2 and PDGFRA mRNA, reduced numbers of NG2‐, Olig2‐ and HDAC2‐immunoreactive cells and reduced glucose transporter immunoreactivity. Partial recovery of some of these markers occurred at stages V–VI/B–C.ConclusionsThe present observations demonstrate that co‐morbidities have an impact on WM integrity in the elderly and in AD, and that early alterations in oligodendrocytes and transcription of genes linked to myelin proteins in WM occur in AD cases without co‐morbidities. These are followed by partial recovery attempts at advanced stages. These observations suggest that oligodendrocytopathy is part of AD.
Highlights
Reduced white matter (WM) volume, WM lesions and altered WM integrity and cortical disconnection occur in the ageing human brain [1,2,3,4,5,6,7,8,9,10]
The density of myelin was significantly reduced in Alzheimer’s disease (AD) without co-morbidities and in AD-Co when compared with MA (P = 0.000 and P = 0.000 respectively)
Regarding AD cases without co-morbidities, no significant differences, but rather a tendency to reduced myelin density was seen in AD stages V–VI when compared with AD stages I–II and AD stages III–IV (Figure 2C)
Summary
Reduced white matter (WM) volume, WM lesions and altered WM integrity and cortical disconnection occur in the ageing human brain [1,2,3,4,5,6,7,8,9,10]. Age-related WM decay is associated with memory impairment and Reduced WM size, WM hyper-lucencies and myelin and axon damage are common in sporadic Alzheimer’s disease (AD), as revealed by neuroimaging methods, mainly magnetic resonance imaging (MRI), and. Breakdown of WM integrity is considered a principal component of AD, contributing to neural disconnection and progression of clinical symptoms and dementia [13]
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