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

Anna M Pietroboni, Marta Scarioni, Tiziana Carandini, Paola Basilico, Marcello Cadioli, Giovanni Giulietti, Andrea Arighi, Michela Caprioli, Laura Serra, Clara Sina, Chiara Fenoglio, Laura Ghezzi, Giorgio G Fumagalli, Milena A De Riz, Alberto Calvi, Fabio Triulzi, Marco Bozzali, Elio Scarpini, Daniela Galimberti

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalJournal of Neurology, Neurosurgery and Psychiatry
DOIs
Publication statusE-pub ahead of print - Oct 20 2017

Keywords

  • Journal Article

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