The molecular spectrum of amyloid‐beta (Aβ) in neurodegenerative diseases beyond Alzheimer's disease
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Bibliographic record
Abstract
Abstract This study investigated the molecular spectrum of amyloid‐beta (Aβ) in neurodegenerative diseases beyond Alzheimer's disease (AD). We analyzed Aβ deposition in the temporal cortex and striatum in 116 autopsies, including Lewy body disease (LBD; N = 51), multiple system atrophy (MSA; N = 10), frontotemporal lobar degeneration‐TDP‐43 (FTLD‐TDP; N = 16), and progressive supranuclear palsy (PSP; N = 39). The LBD group exhibited the most Aβ deposition in the temporal cortex and striatum (90/76%, respectively), followed by PSP (69/28%), FTLD‐TDP (50/25%), and the MSA group (50/10%). We conducted immunohistochemical analysis using antibodies targeting eight Aβ epitopes in the LBD and PSP groups. Immunohistochemical findings were evaluated semi‐quantitatively and quantitatively using digital pathology. Females with LBD exhibited significantly more severe Aβ deposition, particularly Aβ 42 and Aβ 43 , along with significantly more severe tau pathology. Furthermore, a quantitative analysis of all Aβ peptides in the LBD group revealed an association with the APOE‐ ε4 genotypes. No significant differences were observed between males and females in the PSP group. Finally, we compared striatal Aβ deposition in cases with LBD ( N = 15), AD without α‐synuclein pathology ( N = 6), and PSP ( N = 5). There were no differences in the pan‐Aβ antibody (6F/3D)‐immunolabeled deposition burden among the three groups, but the deposition burden of peptides with high aggregation capacity, especially Aβ 43 , was significantly higher in the AD and LBD groups than in the PSP group. Furthermore, considerable heterogeneity was observed in the composition of Aβ peptides on a case‐by‐case basis in the AD and LBD groups, whereas it was relatively uniform in the PSP group. Cluster analysis further supported these findings. Our data suggest that the type of concomitant proteinopathies influences the spectrum of Aβ deposition, impacted also by sex and APOE genotypes.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it