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

Pietroboni, Anna M, Scarioni, Marta, Carandini, Tiziana, Basilico, Paola, Cadioli, Marcello, Giulietti, Giovanni, Arighi, Andrea, Caprioli, Michela, Serra, Laura, Sina, Clara, Fenoglio, Chiara, Ghezzi, Laura, Fumagalli, Georgio G, De Riz, Milena A, Calvi, Alberto, Triulzi, Fabio, Bozzali, Marco, Scarpini, Elio and Galimberti, Daniela (2017) CSF β-amyloid and white matter damage: a new perspective on Alzheimer's disease. Journal of Neurology, Neurosurgery and Psychiatry. ISSN 0022-3050

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Abstract

Objective: To assess the connection between amyloid pathology and white matter (WM) macro- and micro-structural 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 (MCI), and 20 age- and sex-matched heatlhy controls. β-amyloid1-42 (Aβ) levels were determined in cerebrospinal fluid (CSF) samples from all patients and 5 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 magnetic resonance imaging (MRI). We used T2-weighted scans to quantify white matter (WM) lesion loads (LL), and diffusion weighted images (DWI) 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 to both, healthy controls (p=0.003) and Aβ(-) patients (p=0.02). Interestingly, CSF Aβ concentration was the best predictor patients’ WM-LL (r=-0.30, p<0.05) when using age as a covariate. Lesion apparent diffusion coefficient (ADC) 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 Alzheimer’s disease (AD) pathogenesis. The correlation between CSF Aβ levels and WM-LL suggests a direct link between amyloid pathology and WM macro- and microstructural damage.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
Subjects: R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
Depositing User: Patricia Butler
Date Deposited: 02 Oct 2017 14:14
Last Modified: 23 Oct 2017 10:00
URI: http://sro.sussex.ac.uk/id/eprint/70393

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