Department of Psychiatry investigators focused on Alzheimer’s Research—Victor Villemagne, MD (Professor of Psychiatry); Tharick Pascoal, MD, PhD (Associate Professor of Psychiatry and Neurology); and Thomas Karikari, PhD (Assistant Professor of Psychiatry)—have recently published studies improving our understanding of biomarkers for Alzheimer’s disease.
Plasma Glial Fibrillary Acidic Protein Is Associated with 18F-SMBT-1 PET: Two Putative Astrocyte Reactivity Biomarkers for Alzheimer’s Disease (senior corresponding author: Dr. Villemagne)
Astrocyte reactivity is an early event along the Alzheimer’s disease continuum. Plasma glial fibrillary acidic protein (GFAP), posited to reflect astrocyte reactivity, is elevated across the Alzheimer’s disease continuum from preclinical to dementia stages. Monoamine oxidase-B (MAO-B) is also elevated in GFAP+ reactive astrocytes observed using 18F-SMBT-1 PET in Alzheimer’s disease. A team of scientists examined whether plasma GFAP and 18F-SMBT-1 PET are associated, accounting for soluble Amyloid-β (Aβ) and/or aggregated Aβ (Aβ PET). Results of the study showed an association between plasma GFAP and regional 18F-SMBT-1 PET, which appears to be dependent on brain Aβ load.
Chatterjee P, Doré V, Pedrini S, Krishnadas N, Thota R, Bourgeat P, Ikonomovic MD, Rainey-Smith SR, Burnham SC, Fowler C, Taddei K, Mulligan R, Ames D, Masters CL, Fripp J, Rowe CC, Martins RN, Villemagne V, and for the AIBL Research Group.
Journal of Alzheimer’s Disease, vol. 92, no. 2, pp. 615-628, 2023
Blood-brain barrier integrity impacts the use of plasma amyloid-β as a proxy of brain amyloid-β pathology (senior corresponding author: Dr. Pascoal)
Although amyloid-β (Aβ) and tau can be quantified in blood, biological factors can influence the levels of brain-derived proteins in the blood and limit the performance of Alzheimer’s disease plasma biomarkers. To determine whether blood-brain barrier altered permeability might affect the relationship between brain and blood biomarkers, investigators evaluated the impact of blood-brain barrier permeability, as measured by the widely applied cerebrospinal fluid/serum albumin ratio, on the associations between plasma, cerebrospinal fluid, and imaging Alzheimer’s disease core biomarkers across the aging and Alzheimer’s disease spectrum. They found that blood-brain barrier permeability affects the association between brain and plasma Aβ levels, but not the association between brain and plasma p-tau levels. In addition, the findings included that blood-brain barrier permeability increases with age but not according to cognitive status.
Bellaver B, Puig-Pijoan A, Ferrari-Souza JP, Leffa DT, Lussier FZ, Ferreira PCL, Tissot C, Povala G, Therriault J, Benedet AL, Ashton NJ, Servaes S, Chamoun M, Stevenson J, Rahmouni N, Vermeiren M, Macedo AC, Fernández-Lebrero A, García-Escobar G, Navalpotro-Gómez I, Lopez O, Tudorascu DL, Cohen A, Villemagne VL, Klunk WE, Gauthier S, Zimmer ER, Karikari TK, Blennow K, Zetterberg H, Suárez-Calvet M, Rosa-Neto P, Pascoal TA.
Alzheimer’s & Dementia.2023;1-11.https://doi.org/10.1002/alz.13014
Plasma biomarkers identify older adults at risk of Alzheimer’s disease and related dementias in a real-world population-based cohort (senior corresponding author: Dr. Karikari)
Plasma biomarkers—cost effective, non-invasive indicators of Alzheimer’s disease and related disorders—have primarily been studied in clinical research cohorts with cerebrospinal fluid/neuroimaging biomarkers categorization, lacking heterogeneity of social, economic, and geographic origins. Investigators examined plasma biomarker profiles and their associated factors in a well-characterized community-based cohort to determine whether they could identify an at-risk group independently of brain and cerebrospinal fluid biomarkers. Study participants were clustered into groups defined by plasma amyloid beta (Aβ)42/40 ratio levels: abnormal, uncertain, and normal. The investigators found that abnormal plasma Aβ42/40 ratio identified older adult groups with lower memory scores, higher dementia risks, and higher Alzheimer’s disease and related disorders biomarker levels, with potential implications for population screening.
Ferreira PCL, Zhang Y, Snitz B, Chang CH, Bellaver B, Jacobsen E, Kamboh MI, Zetterberg H, Blennow K, Pascoal TA, Villemagne VL, Ganguli M, Karikari TK.
Alzheimer’s & Dementia. 2023; 1- 13. https://doi.org/10.1002/alz.12986