Journal of Alzheimer's Disease - Volume 73, issue 4

Authors: Mold, Matthew | Linhart, Caroline | Gómez-Ramírez, Johana | Villegas-Lanau, Andrés | Exley, Christopher

Article Type: Research Article

Abstract: Genetic predispositions associated with metabolism of the amyloid-β protein precursor underlie familial Alzheimer’s disease; a form of dementia characterized by early disease onset and elevated levels of cortical amyloid-β. Human exposure to aluminum is linked to the etiology of Alzheimer’s disease and recent research measured a high content of aluminum in brain tissue in familial Alzheimer’s disease. To elaborate upon this finding, we have obtained brain tissues from a Colombian cohort of donors with familial Alzheimer’s disease. We have used established methods to measure the aluminum content of these tissues and we have compared the data with a recently measured …dataset for control brain tissues. We report significantly higher levels of aluminum in brain tissues in donors with familial Alzheimer’s disease than in control tissues from donors without neurological impairment or neurodegeneration. We have used aluminum-specific fluorescence microscopy along with complementary imaging for amyloid-β to demonstrate a very high degree of co-localization of these two risk factors in brain tissue in familial Alzheimer’s disease. Aluminum and amyloid-β were co-located in senile plaques as well as vasculature, the latter resembling cerebral amyloid angiopathy. Aluminum was also found separately from amyloid-β in intracellular compartments including glia and neuronal axons. The research has identified an arguably unique association between high brain aluminum content and amyloid-β and allows postulation that genetic predispositions defining familial Alzheimer’s disease underlie this relationship. Show more

Keywords: Aluminum in human brain tissue, amyloid-β, familial Alzheimer’s disease, human exposure to aluminum

DOI: 10.3233/JAD-191140

Citation: Journal of Alzheimer's Disease, vol. 73, no. 4, pp. 1627-1635, 2020

Authors: Furman, Ran | Ng, Sharon C.W. | Komatsu, Hiroaki | Axelsen, Paul H.

Article Type: Research Article

Abstract: Various amyloid-β (Aβ) peptides accumulate in brain in Alzheimer’s disease, and the amounts of specific peptide variants may have pathological significance. The quantitative determination of these variants is challenging because losses inevitably occur during tissue processing and analysis. This report describes the use of stable-isotope-labeled Aβ peptides as internal standards for quantitative mass spectrometric assays, and the use of cyanogen bromide (CNBr) to remove C-terminal residues beyond Met35. The removal of residues beyond Met35 reduces losses due to aggregation, and facilitates the detection of post-translationally modified Aβ peptides. Results from 8 human brain samples suggest that the tissue concentrations of …the 42-residue Aβ peptide tend to be similar in different patients. Concentrations of the 40-residue Aβ peptide are more variable, and may be greater or lesser than the 42-residue peptide. The concentration of the CNBr cleavage product closely matches the sum of the 40-residue and 42-residue peptide concentrations, indicating that these two Aβ peptides account for most of the C-terminal variants in these patients. CNBr treatment facilitated the detection of post-translational modifications such as pyroglutamyl and hexose-modified Aβ peptides. Show more

Keywords: Immunoprecipitation, internal standards, isotope labeling, post-translational modification

DOI: 10.3233/JAD-190647

Citation: Journal of Alzheimer's Disease, vol. 73, no. 4, pp. 1637-1645, 2020

Authors: Spallazzi, Marco | Michelini, Giovanni | Barocco, Federica | Dieci, Francesca | Copelli, Sandra | Messa, Giovanni | Scarlattei, Maura | Pavesi, Giovanni | Ruffini, Livia | Caffarra, Paolo

Article Type: Research Article

Abstract: Background: Free and Cued Selective Reminding Test (FCSRT) is a reliable cognitive marker for Alzheimer’s disease (AD), and the identification of neuropsychological tests sensitive to the early signs of AD pathology is crucial both in research and clinical practice. Objective: The study aimed to ascertain the ability of FCSRT in predicting the amyloid load as determined from amyloid PET imaging (Amy-PET) in patients with cognitive disorders. Methods: For our purpose, 79 patients (71 MCI, 8 mild dementia) underwent a complete workup for dementia, including the FCSRT assessment and a [18 F]florbetaben PET scan. FCSRT subitem scores …were used as predictors in different binomial regression models. Results: Immediate free recall and delayed free recall were the best predictors overall in the whole sample; whereas in patients <76 years, all models further improved with immediate total recall (ITR) and Index of Sensitivity of Cueing (ISC) resulting the most accurate in anticipating Amy-PET results, with a likelihood of being Amy-PET positive greater than 85% for ITR and ISC scores of less than 25 and 0.5, respectively. Conclusion: FCSRT proved itself to be a valid tool in dementia diagnosis, also being able to correlate with amyloid pathology. The possibility to predict Amy-PET results through a simple and reliable neuropsychological test might be helpful for clinicians in the dementia field, adding value to a paper and pencil tool compared to most costly biomarkers. Show more

Keywords: Alzheimer’s disease, amyloid PET, biomarkers, Free and Cued Selective Reminding Test, mild cognitive impairment, neuropsychology

DOI: 10.3233/JAD-190950

Citation: Journal of Alzheimer's Disease, vol. 73, no. 4, pp. 1647-1659, 2020