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-amyloid 1-42 (Aβ) levels were determined in cerebrospinal fluid (CSF) samples from all patients and 5 controls. Among patients, 42had 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.

mRNFL, mGCL, and mIPL are significantly reduced in MS patients without concomitant pRNFL thinning. These retinal changes show a significant association with cortical regions that are known to be important for visuospatial performance.

Background: The importance of predicting disease progression in multiple sclerosis (MS) has increasingly been recognised, hence reliable biomarkers are needed.Objectives: To investigate the prognostic role of cerebrospinal fluid (CSF) Amyloid beta1-42 (A) levels by the determination of a cut-off value to classify patients in slow and fast progressors. To evaluate possible association with white (WM) and grey matter (GM) damage at early disease stages.Methods: Sixty patients were recruited and followed-up for three to five years. Patients underwent clinical assessment, CSF analysis to determine Aβ levels, and brain MRI (at baseline and after 1 year). T1-weighted volumes were calculated. T2-weighted scans were used to quantify WM lesion loads.Results: Lower CSF Aβ levels were observed in patients with a worse follow-up EDSS (r=−0.65, p<0.001).The multiple regression analysis confirmed CSF Aβ concentration as a predictor of patients' EDSS increase (r=−0.59, p<0.0001). Generating a receiver operator characteristic curve, a cut-off value of 813 pg/ml was determined as the threshold able to identify patients with worse prognosis (95%CI 0.690-0.933, p=0.0001). No differences in CSF tau and NfL levels were observed (p>0.05).Conclusions: Low CSF Aβ levels may represent a predictive biomarker of disease progression in MS.