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Research paper
CSF β-amyloid and white matter damage: a new perspective on Alzheimer’s disease
  1. Anna M Pietroboni1,
  2. Marta Scarioni1,
  3. Tiziana Carandini1,
  4. Paola Basilico1,
  5. Marcello Cadioli2,
  6. Giovanni Giulietti3,
  7. Andrea Arighi1,
  8. Michela Caprioli1,
  9. Laura Serra3,
  10. Clara Sina2,
  11. Chiara Fenoglio1,
  12. Laura Ghezzi1,
  13. Giorgio G Fumagalli1,
  14. Milena A De Riz1,
  15. Alberto Calvi1,
  16. Fabio Triulzi2,
  17. Marco Bozzali3,4,
  18. Elio Scarpini1,
  19. Daniela Galimberti1
  1. 1Department of Pathophysiology and Transplantation, Neurodegenerative Disease Unit, University of Milan, Centro Dino Ferrari, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
  2. 2Department of Pathophysiology and Transplantation, Neuroradiology Unit, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
  3. 3Neuroimaging Laboratory, Santa Lucia Foundation IRCCS, Rome, Italy
  4. 4Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK
  1. Correspondence to Dr Anna M Pietroboni, Department of Pathophysiology and Transplantation, Neurology Unit, University of Milan, Centro Dino Ferrari, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan 20122, Italy; pb.anna{at}


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.

  • multiple sclerosis
  • myelin
  • neroimmunology
  • neuroradiology
  • dementia

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  • Contributors AMP: design of the study, analysis and interpretation of the data and drafting the manuscript. MS, TC and PB: analysis and interpretation of the data and drafting the manuscript. MC, GG, AA, LS, CS and CF: analysis of the data. MC: analysis of the data and minor contribution to draft the manuscript. LG, GGF and MADR: minor contribution to analysis of the data. FT and ES: revising the manuscript for intellectual content. MB and DG: drafting and revising the manuscript for intellectual content.

  • Funding This research was supported by the Italian Ministry of Health (Ricerca Corrente to ES).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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