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

被引：49

作者：

Pietroboni, Anna M. ^{[1
]}

Scarioni, Marta ^{[1
]}

Carandini, Tiziana ^{[1
]}

Basilico, Paola ^{[1
]}

Cadioli, Marcello ^{[2
]}

Giulietti, Giovanni ^{[3
]}

Arighi, Andrea ^{[1
]}

Caprioli, Michela ^{[1
]}

Serra, Laura ^{[3
]}

Sina, Clara ^{[2
]}

Fenoglio, Chiara ^{[1
]}

Ghezzi, Laura ^{[1
]}

Fumagalli, Giorgio G. ^{[1
]}

De Riz, Milena A. ^{[1
]}

Calvi, Alberto ^{[1
]}

Triulzi, Fabio ^{[2
]}

Bozzali, Marco ^{[3
,4
]}

Scarpini, Elio ^{[1
]}

Galimberti, Daniela ^{[1
]}

机构：

[1] Univ Milan, Dept Pathophysiol & Transplantat, Neurodegenerat Dis Unit, Ctr Dino Ferrari,Fdn Ca Granda,IRCCS,Osped Maggio, Milan, Italy

[2] Univ Milan, Dept Pathophysiol & Transplantat, Neuroradiol Unit, Fdn Ca Granda,IRCCS,Osped Maggiore Policlin, Milan, Italy

[3] Santa Lucia Fdn, IRCCS, Neuroimaging Lab, Rome, Italy

[4] Univ Sussex, Brighton & Sussex Med Sch, Dept Neurosci, Brighton, E Sussex, England

来源：

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY | 2018年 / 89卷 / 04期

关键词：

VASCULAR COGNITIVE IMPAIRMENT; MR SIGNAL ABNORMALITIES; FRONTOTEMPORAL DEMENTIA; HYPERINTENSITIES; PATHOPHYSIOLOGY; HETEROGENEITY; PROGRANULIN; MUTATION; LESIONS; MEMORY;

D O I：

10.1136/jnnp-2017-316603

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

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. beta-amyloid 1-42 (A beta) levels were determined in cerebrospinal fluid (CSF) samples from all patients and five controls. Among patients, 42 had pathological CSF A beta levels (A beta(+)), while 23 had normal CSF A beta levels (A beta(-)). 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 A beta(+) compared with both, healthy controls (p=0.003) and A beta(-) patients (p=0.02). Interestingly, CSF A beta 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 A beta(+), 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 A beta levels and WM-LL suggests a direct link between amyloid pathology and WM macrostructural and microstructural damage.

引用

页码：352 / 357

页数：6

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