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- Snellman, Anniina, et al.
(author)
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APOE epsilon 4 gene dose effect on imaging and blood biomarkers of neuroinflammation and beta-amyloid in cognitively unimpaired elderly
- 2023
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In: Alzheimers Research & Therapy. - 1758-9193. ; 15:1
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Journal article (peer-reviewed)abstract
- BackgroundNeuroinflammation, characterized by increased reactivity of microglia and astrocytes in the brain, is known to be present at various stages of the Alzheimer's disease (AD) continuum. However, its presence and relationship with amyloid pathology in cognitively normal at-risk individuals is less clear. Here, we used positron emission tomography (PET) and blood biomarker measurements to examine differences in neuroinflammation and beta-amyloid (A beta) and their association in cognitively unimpaired homozygotes, heterozygotes, or non-carriers of the APOE epsilon 4 allele, the strongest genetic risk for sporadic AD.MethodsSixty 60-75-year-old APOE epsilon 4 homozygotes (n = 19), heterozygotes (n = 21), and non-carriers (n = 20) were recruited in collaboration with the local Auria biobank. The participants underwent C-11-PK11195 PET (targeting 18-kDa translocator protein, TSPO), C-11-PiB PET (targeting A beta), brain MRI, and neuropsychological testing including a preclinical cognitive composite (APCC). C-11-PK11195 distribution volume ratios and C-11-PiB standardized uptake value ratios (SUVRs) were calculated for regions typical for early A beta accumulation in AD. Blood samples were drawn for measuring plasma glial fibrillary acidic protein (GFAP) and plasma A beta(1-42/1.40).ResultsIn our cognitively unimpaired sample, cortical C-11-PiB-binding increased according to APOE epsilon 4 gene dose (median composite SUVR 1.47 (range 1.38-1.66) in non-carriers, 1.55 (1.43-2.02) in heterozygotes, and 2.13 (1.61-2.83) in homozygotes, P = 0.002). In contrast, cortical composite C-11-PK11195-binding did not differ between the APOE epsilon 4 gene doses (P = 0.27) or between A beta-positive and A beta-negative individuals (P = 0.81) and associated with higher A beta burden only in APOE epsilon 4 homozygotes (Rho = 0.47, P = 0.043). Plasma GFAP concentration correlated with cortical C-11-PiB (Rho = 0.35, P = 0.040), but not C-11-PK11195-binding (Rho = 0.13, P = 0.47) in A beta-positive individuals. In the total cognitively unimpaired population, both higher composite C-11-PK11195-binding and plasma GFAP were associated with lower hippocampal volume, whereas elevated C-11-PiB-binding was associated with lower APCC scores.ConclusionsOnly A beta burden measured by PET, but not markers of neuroinflammation, differed among cognitively unimpaired elderly with different APOE epsilon 4 gene dose. However, APOE epsilon 4 gene dose seemed to modulate the association between neuroinflammation and A beta.
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| 2. |
- Snellman, Anniina, et al.
(author)
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Head-to-head comparison of plasma p-tau181, p-tau231 and glial fibrillary acidic protein in clinically unimpaired elderly with three levels of APOE4-related risk for Alzheimer's disease
- 2023
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In: Neurobiology of Disease. - 0969-9961. ; 183
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Journal article (peer-reviewed)abstract
- Plasma phosphorylated tau (p-tau) and glial fibrillary acidic protein (GFAP) both reflect early changes in Alzheimer's disease (AD) pathology. Here, we compared the biomarker levels and their association with regional S-amyloid (AS) pathology and cognitive performance head-to-head in clinically unimpaired elderly (n = 88) at three levels of APOE4-related genetic risk for sporadic AD (APOE4/4 n = 19, APOE3/4 n = 32 or non-carriers n = 37). Concentrations of plasma p-tau181, p-tau231 and GFAP were measured using Single molecule array (Simoa), regional AS deposition with 11C-PiB positron emission tomography (PET), and cognitive performance with a preclinical composite. Significant differences in plasma p-tau181 and p-tau231, but not plasma GFAP concentrations were present between the APOE4 gene doses, explained solely by brain AS load. All plasma biomarkers correlated positively with AS PET in the total study population. This correlation was driven by APOE3/3 carriers for plasma p-tau markers and APOE4/4 carriers for plasma GFAP. Voxel-wise associations with amyloid-PET revealed different spatial patterns for plasma p-tau markers and plasma GFAP. Only higher plasma GFAP correlated with lower cognitive scores. Our observations suggest that plasma p-tau and plasma GFAP are both early AD markers reflecting different AS-related processes.
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