P2–205: Butyrylcholinesterase‐associated neuropathology in early‐onset familial Alzheimer's disease
Bibliographic record
Abstract
Early-onset familial Alzheimer's disease (FAD) is characterized as an uncommon form of AD affecting genetically predisposed individuals before age 65. Details of neuropathological data concerning FAD mutations of genes encoding for presenilin-1 (PS1) are limited, particularly for the mutation Leu235Pro occurring in the TM5 domain of PS1. Butyrylcholinesterase (BuChE) is an enzyme involved in the regulation of cholinergic neurotransmission and is found in association with β-amyloid (Aβ) plaques and tau neurofibrillary tangles (NFTs) in AD. We hypothesized, as with sporadic AD, BuChE is associated with these AD neuropathological hallmarks in FAD. Post-mortem brain tissues from three FAD cases with the PS1 mutation Leu235Pro and one case with confirmed sporadic AD were examined. Adjacent sections of brain tissues were stained with Aβ and tau immunohistochemical methods and thioflavin-S and BuChE histochemical methods. All brains were given an “ABC” score using the National Institute on Aging-Alzheimer's Association neuropathology guidelines for AD. Plaque loads in select regions were quantified using NIH ImageJ software and recorded as a percentage of the total area. All cases demonstrated severe dementia (Global Deterioration Scale scores = 6) prior to death. AD pathology was prominent throughout the rostrocaudal extent of all four brains; ABC scores revealed high neuropathological change. In FAD cases, the distribution of neuronal BuChE paralleled that in normal human tissue and was associated with Aβ plaques and NFTs, as previously described in sporadic AD. Of note was the abundance of Aβ-, BuChE- and thioflavin-S-positive plaques. Plaque density was most notable with Aβ staining, followed by subsequent decreases of BuChE and thioflavin-S plaque staining. The Leu235Pro substitution of the PSEN1 gene produces significant behavioral and pathological impairment, with onset typically before 40 years of age. As reported in cases of sporadic AD, these findings confirm that BuChE is highly associated with AD pathology in this mutation and may be involved in the maturation of toxic Aβ protofibrils. This enzyme may hold promise as a therapeutic and neuroimaging target in AD, particularly in cases of aggressive FAD forms.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".