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-amyloid 1-42 (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(â ')). 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(â ') patients (p=0.02). Interestingly, CSF Aβ concentration was the best predictor of patients' WM-LL (r=â '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.

CSF β-amyloid and white matter damage: A new perspective on Alzheimer's disease / Pietroboni, A. M.; Scarioni, M.; Carandini, T.; Basilico, P.; Cadioli, M.; Giulietti, G.; Arighi, A.; Caprioli, M.; Serra, L.; Sina, C.; Fenoglio, C.; Ghezzi, L.; Fumagalli, G. G.; De Riz, M. A.; Calvi, A.; Triulzi, F.; Bozzali, M.; Scarpini, E.; Galimberti, D.. - In: JOURNAL OF NEUROLOGY, NEUROSURGERY AND PSYCHIATRY. - ISSN 0022-3050. - 89:4(2018), pp. 352-357. [10.1136/jnnp-2017-316603]

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

Fumagalli G. G.;
2018-01-01

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-amyloid 1-42 (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(â ')). 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(â ') patients (p=0.02). Interestingly, CSF Aβ concentration was the best predictor of patients' WM-LL (r=â '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.
2018
4
Pietroboni, A. M.; Scarioni, M.; Carandini, T.; Basilico, P.; Cadioli, M.; Giulietti, G.; Arighi, A.; Caprioli, M.; Serra, L.; Sina, C.; Fenoglio, C.;...espandi
CSF β-amyloid and white matter damage: A new perspective on Alzheimer's disease / Pietroboni, A. M.; Scarioni, M.; Carandini, T.; Basilico, P.; Cadioli, M.; Giulietti, G.; Arighi, A.; Caprioli, M.; Serra, L.; Sina, C.; Fenoglio, C.; Ghezzi, L.; Fumagalli, G. G.; De Riz, M. A.; Calvi, A.; Triulzi, F.; Bozzali, M.; Scarpini, E.; Galimberti, D.. - In: JOURNAL OF NEUROLOGY, NEUROSURGERY AND PSYCHIATRY. - ISSN 0022-3050. - 89:4(2018), pp. 352-357. [10.1136/jnnp-2017-316603]
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