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

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)352-357
Number of pages6
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume89
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

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Amyloid
Cerebrospinal Fluid
Alzheimer Disease
White Matter
Pathology
Neurologic Examination
Dementia
Regression Analysis
Brain

Keywords

  • dementia
  • multiple sclerosis
  • myelin
  • neroimmunology
  • neuroradiology

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

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, Giorgio G.; De Riz, Milena A.; Calvi, Alberto; Triulzi, Fabio; Bozzali, Marco; Scarpini, Elio; Galimberti, Daniela.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 89, No. 4, 01.04.2018, p. 352-357.

Research output: Contribution to journalArticle

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, Giorgio G. ; De Riz, Milena A. ; Calvi, Alberto ; Triulzi, Fabio ; Bozzali, Marco ; Scarpini, Elio ; Galimberti, Daniela. / CSF β-amyloid and white matter damage : A new perspective on Alzheimer's disease. In: Journal of Neurology, Neurosurgery and Psychiatry. 2018 ; Vol. 89, No. 4. pp. 352-357.
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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({\^a} ')). 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({\^a} ') patients (p=0.02). Interestingly, CSF Aβ concentration was the best predictor of patients' WM-LL (r={\^a} '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.",
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T1 - CSF β-amyloid and white matter damage

T2 - A new perspective on Alzheimer's disease

AU - Pietroboni, Anna M.

AU - Scarioni, Marta

AU - Carandini, Tiziana

AU - Basilico, Paola

AU - Cadioli, Marcello

AU - Giulietti, Giovanni

AU - Arighi, Andrea

AU - Caprioli, Michela

AU - Serra, Laura

AU - Sina, Clara

AU - Fenoglio, Chiara

AU - Ghezzi, Laura

AU - Fumagalli, Giorgio G.

AU - De Riz, Milena A.

AU - Calvi, Alberto

AU - Triulzi, Fabio

AU - Bozzali, Marco

AU - Scarpini, Elio

AU - Galimberti, Daniela

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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.

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KW - multiple sclerosis

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