Neuropathology of Alzheimer´s disease in vivo: relationship between neuroimaging measures (positron emission tomography and magnetic resonance imaging) and novel plasma biomarkers

• Grant number: 25/06065-4
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2026
• End date: February 28, 2029
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Geraldo Busatto Filho
• Grantee: Geraldo Busatto Filho
• Host Institution: Instituto de Psiquiatria Doutor Antonio Carlos Pacheco e Silva (IPq). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Carlos Alberto Buchpiguel ; Daniele de Paula Faria ; Fábio Henrique de Gobbi Porto ; Fábio Luís de Souza Duran ; Leda Leme Talib

Abstract

In the last decades, several biomarkers for the diagnosis of Alzheimer´s disease (AD) in vivo have been validated, including cerebrospinal fluid (CSF) measurements of fragments of beta amyloid peptide (A¿) and tau protein, positron emission tomography (PET) findings of A¿ or tau deposits and regional brain glucose hypometabolism, and magnetic resonance imaging (MRI) findings of reduced regional volume and cortical thickness in the brain. Recently, single molecule arrays for ultrasensitive protein detection (SIMOA) have also enabled the development of plasma biomarkers (PBs) for the diagnosis of AD, with potential for high reliability and equivalent accuracy in comparison with CSF measurements of A¿ e tau fragments, and indices of neurodegeneration. Since PBs provide only indirect measures that reflect the status of AD pathological changes at a given point in time, it is critical to conduct research studies to evaluate the relationship between these PBs and the neuroimaging methods (PET and MRI) that directly map the neuropathology of AD in its topographic progression over the course of the disease. With an expected sample size of 240 elderly subjects (with dementia clinically compatible with AD, amnestic mild cognitive impairment or intact cognition), the present project proposes 5 lines of investigation of inter-relationships between imaging markers (cortical thickness, A¿ deposition and glucose metabolism) versus a comprehensive panel of 9 PBs, analyzed using plasma aliquots collected in proximity with the date when the radiological data was collected. The results aim to advance knowledge on how measurements of each PB associates with specific and localized neuroimaging changes, and the extent to which combinations of PBs are related to the magnitude and spatial distribution of such brain abnormalities. (AU)