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J Neurol Neurosurg Psychiatry. 2018 Apr;89(4):352-357. doi: 10.1136/jnnp-2017-316603. Epub 2017 Oct 20.

CSF β-amyloid and white matter damage: a new perspective on Alzheimer's disease.

Author information

1
Department of Pathophysiology and Transplantation, Neurodegenerative Disease Unit, University of Milan, Centro Dino Ferrari, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
2
Department of Pathophysiology and Transplantation, Neuroradiology Unit, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
3
Neuroimaging Laboratory, Santa Lucia Foundation IRCCS, Rome, Italy.
4
Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.

Abstract

OBJECTIVE:

To assess the connection between amyloid pathology and white matter (WM) macrostructural and microstructural damage in demented patients compared with controls.

METHODS:

Eighty-five participants were recruited: 65 with newly diagnosed Alzheimer's disease (AD), non-AD dementia or mild cognitive impairment and 20 age-matched and sex-matched healthy controls. β-amyloid1-42 (Aβ) levels were determined in cerebrospinal fluid (CSF) samples from all patients and five controls. Among patients, 42 had pathological CSF Aβ levels (Aβ(+)), while 23 had normal CSF Aβ levels (Aβ(-)). All participants underwent neurological examination, neuropsychological testing and brain MRI. We used T2-weighted scans to quantify WM lesion loads (LLs) and diffusion-weighted images to assess their microstructural substrate. Non-parametric statistical tests were used for between-group comparisons and multiple regression analyses.

RESULTS:

We found an increased WM-LL in Aβ(+) compared with both, healthy controls (p=0.003) and Aβ(-) patients (p=0.02). Interestingly, CSF Aβ concentration was the best predictor of patients' WM-LL (r=-0.30, p<0.05) when using age as a covariate. Lesion apparent diffusion coefficient value was higher in all patients than in controls (p=0.0001) and correlated with WM-LL (r=0.41, p=0.001). In Aβ(+), WM-LL correlated with WM microstructural damage in the left peritrigonal WM (p<0.0001).

CONCLUSIONS:

WM damage is crucial in AD pathogenesis. The correlation between CSF Aβ levels and WM-LL suggests a direct link between amyloid pathology and WM macrostructural and microstructural damage.

KEYWORDS:

dementia; multiple sclerosis; myelin; neroimmunology; neuroradiology

PMID:
29054920
DOI:
10.1136/jnnp-2017-316603

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