Longitudinal brain atrophy and CSF biomarkers in early-onset Alzheimer’s disease

• Published in: NeuroImage clinical Vol. 32; p. 102804
• Main Authors: Contador, José, Pérez-Millán, Agnès, Tort-Merino, Adrià, Balasa, Mircea, Falgàs, Neus, Olives, Jaume, Castellví, Magdalena, Borrego-Écija, Sergi, Bosch, Beatriz, Fernández-Villullas, Guadalupe, Ramos-Campoy, Oscar, Antonell, Anna, Bargalló, Nuria, Sanchez-Valle, Raquel, Sala-Llonch, Roser, Lladó, Albert
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2021; Elsevier
• Subjects: Alzheimer Disease - diagnostic imaging; Alzheimer Disease - pathology; Amyloid beta-Peptides; Atrophy; Atrophy - pathology; Biomarkers; Brain - diagnostic imaging; Brain - pathology; Cerebrospinal fluid; Early-onset Alzheimer's disease; Humans; Longitudinal; Magnetic Resonance Imaging; MRI; Radiology; Regular; tau Proteins; ADNI; MTL; MRI; LOAD; Early-onset Alzheimer's disease; GLM; p-tau; Cerebrospinal fluid; Atrophy; FWE; MMSE; CTh; CSF; NIA-AA; NFT; AD; Bankssts; Longitudinal; Aβ42; GM; HCB; spc; EOAD; MCI; NfL; t-tau; FWHM; Biomarkers; HC; PET; cortical thickness; amyloid β1-42; medial temporal lobe; Alzheimer’s disease Neuroimaging initiative; neurofilament light chain; Alzheimer’s disease; general linear model; cerebrospinal fluid; Mini-Mental State Examination; magnetic resonance imaging; neurofibrillary tangle; late-onset AD; family-wise error; full-width at half maximum; total Tau; Hospital Clinic Barcelona; healthy controls; early-onset AD; phosphorylated Tau; National Institute on Aging-Alzheimer’s Association; banks of the superior temporal sulcus; gray matter; mild cognitive impairment; positron emission tomography; symmetrized percent change
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2021.102804

•Posterior cortices, hippocampus and amygdala track atrophy in EOAD over two years.•The medial temporal cortex is unaltered in EOAD at early stages.•EOAD exhibited a posterior-to-anterior gradient of cortical loss after two years.•EOAD subcortical volume loss extends beyond hippocampus and amygdala after two years.•Cerebrospinal fluid biomarkers might predict atrophy rates in EOAD. There is evidence of longitudinal atrophy in posterior brain areas in early-onset Alzheimer’s disease (EOAD; aged < 65 years), but no studies have been conducted in an EOAD cohort with fluid biomarkers characterization. We used 3T-MRI and Freesurfer 6.0 to investigate cortical and subcortical gray matter loss at two years in 12 EOAD patients (A + T + N + ) compared to 19 controls (A-T-N-) from the Hospital Clínic Barcelona cohort. We explored group differences in atrophy patterns and we correlated atrophy and baseline CSF-biomarkers levels in EOAD. We replicated the correlation analyses in 14 EOAD (A + T + N + ) and 55 late-onset AD (LOAD; aged ≥ 75 years; A + T + N + ) participants from the Alzheimer's disease Neuroimaging Initiative. We found that EOAD longitudinal atrophy spread with a posterior-to-anterior gradient and beyond hippocampus/amygdala. In EOAD, higher initial CSF NfL levels correlated with higher ventricular volumes at baseline. On the other hand, higher initial CSF Aβ42 levels (within pathological range) predicted higher rates of cortical loss in EOAD. In EOAD and LOAD subjects, higher CSF t-tau values at baseline predicted higher rates of subcortical atrophy. CSF p-tau did not show any significant correlation. In conclusion, posterior cortices, hippocampus and amygdala capture EOAD atrophy from early stages. CSF Aβ42 might predict cortical thinning and t-tau/NfL subcortical atrophy.