Journal of Alzheimer's Disease - Volume 95, issue 2

Authors: Kobro-Flatmoen, Asgeir | Hormann, Thea Meier | Gouras, Gunnar

Article Type: Research Article

Abstract: Background: Amyloid-β (Aβ) is a normal product of neuronal activity, including that of the aggregation-prone Aβ42 variant that is thought to cause Alzheimer’s disease (AD). Much knowledge about AD comes from studies of transgenic rodents expressing mutated human amyloid-β protein precursor (AβPP) to increase Aβ production or the Aβ42/40 ratio. Yet, little is known about the normal expression of Aβ42 in rodent brains. Objective: To characterize the brain-wide expression of Aβ42 throughout the life span of outbred Wistar rats, and to relate these findings to brains of human subjects without neurological disease. …Methods: Aβ42 immunolabeling of 12 Wistar rat brains (3–18 months of age) and brain sections from six human subjects aged 20–88 years. Results: In healthy Wistar rats, we find intracellular Aβ42 (iAβ42 ) in neurons throughout the brain at all ages, but levels vary greatly between brain regions. The highest levels are in neurons of entorhinal cortex layer II, alongside hippocampal neurons at the CA1/subiculum border. Concerning entorhinal cortex layer II, we find similarly high levels of iAβ42 in the human subjects. Conclusion: Expression of iAβ42 in healthy Wistar rats predominates in the same structures where iAβ accumulates and Aβ plaques initially form in the much used, Wistar based McGill-R-Thy1-APP rat model for AD. The difference between wild-type Wistar rats and these AD model rats, with respect to Aβ42 , is therefore quantitative rather that qualitative. This, taken together with our human results, indicate that the McGill rat model in fact models the underlying wild-type neuronal population-specific vulnerability to Aβ42 accumulation. Show more

Keywords: Alzheimer’s disease, animal model, disease onset, entorhinal cortex

DOI: 10.3233/JAD-230349

Citation: Journal of Alzheimer's Disease, vol. 95, no. 2, pp. 719-733, 2023

Authors: Panikkar, Daniel | Vivek, Sithara | Crimmins, Eileen | Faul, Jessica | Langa, Kenneth M. | Thyagarajan, Bharat

Article Type: Research Article

Abstract: Background: Sample collection and preanalytical protocols may significantly impact the results of large-scale epidemiological studies incorporating blood-based biomarkers of neuropathology. Objective: To evaluate the stability and assay variability of several blood-based biomarkers of neuropathology for common preanalytical conditions. Methods: We collected serum and plasma samples from 41 participants and evaluated the effect of processing delay of up to 72 h when stored at 4∘C, three freeze-thaw cycles, and a combination of 48-h processing delay when stored at 4∘C and three freeze-thaw cycles on biomarker stability. Using the Simoa assay (Quanterix Inc.), we measured amyloid-β 40 (Aβ40 ), …amyloid-β 42 (Aβ42 ), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau 181 (p-tau-181). Results: We found that Aβ40 and Aβ42 levels significantly decreased after a 24-h processing delay in both plasma and serum samples, and a single freeze-thaw cycle (p  < 0.0001). Nevertheless, serum Aβ42/40 ratio remained stable with a processing delay up to 48 h while plasma Aβ42/40 ratio showed only small but significant increase with a delay up to 72 h. Both plasma and serum GFAP and NfL levels were only modestly affected by processing delay and freeze-thaw cycles. Plasma p-tau-181 levels notably increased with a 24-, 48-, and 72-h processing delay, but remained stable in serum. Intra-individual variation over two weeks was minimal for all biomarkers and their levels were substantially lower in serum when compared with plasma. Conclusion: These results suggest that standardizing preanalytical variables will allow robust measurements of biomarkers of neuropathology in population studies. Show more

Keywords: Alzheimer’s disease, amyloid-β , blood-based biomarkers, pre-analytical variables, Simoa assay, stability

DOI: 10.3233/JAD-230384

Citation: Journal of Alzheimer's Disease, vol. 95, no. 2, pp. 735-748, 2023

Authors: Perry, George

Article Type: Book Review

DOI: 10.3233/JAD-239008

Citation: Journal of Alzheimer's Disease, vol. 95, no. 2, pp. 749-749, 2023

Article Type: Retraction

DOI: 10.3233/JAD-239009

Citation: Journal of Alzheimer's Disease, vol. 95, no. 2, pp. 751-751, 2023