tools/coverage_map.md

Literature coverage map (2026-08-05)

How much of the FINDABLE literature does the challenge pool actually hold? Nobody had established the denominator, so 'find more papers' was untargeted. This measures it.

Method

For each hypothesis-defining PubMed query, retrieve the full ID list and intersect with the 291 PMIDs the pool has captured. Coverage = pool ∩ slice / slice.

slice	PubMed hits	pool has	coverage	unexamined
microglia + Abeta phagocytosis	1199	43	4%	1156
ABCA1 + APOE (any)	877	63	7%	814
microglia + lipid droplet	334	66	20%	268
ABCA1 + astrocyte	140	30	21%	110
ABCA1 + Alzheimer	330	84	25%	246
APOE4 + microglia + phagocytosis	72	32	44%	40
APOE4 + lipid droplet	56	34	61%	22

Queries are recorded verbatim in the JSON alongside this file so the numbers are reproducible.

Reading it

Tight, clause-specific queries are well covered (APOE4+lipid droplet 61%, APOE4+microglia+ phagocytosis 44%). Broad slices are barely touched (microglia+Abeta phagocytosis 3.6% of 1199). That is the expected shape: agents searched the hypothesis wording, not the surrounding mechanism literature. The gap is real but it is mostly OFF-CLAUSE, so raw unexamined counts overstate the opportunity.

Triage that survives that caveat

179 unexamined papers sit at the intersection of >=2 hypothesis-defining slices; 140 are primary research; 65 are 2018 or later. Scored on endpoint vocabulary:

score	slices	PMID	year	title
11	2	37546938	2023	APOE4/4 is linked to damaging lipid droplets in Alzheimer's microglia.
10	2	39456234	2024	Inhibiting the Cholesterol Storage Enzyme ACAT1/SOAT1 in Myelin Debris-Treated Microglia
9	2	38525390	2024	Investigating the Effect of Aspirin on apoAI-Induced ATP Binding Cassette Transporter 1
7	3	34744007	2022	Amyloid beta increases ABCA1 and HMGCR protein expression, and cholesterol synthesis and
7	2	39840463	2025	Intermittent Fasting Ameliorates β-Amyloid Deposition and Cognitive Impairment Accompani
7	2	37564436	2023	24-Hydroxycholesterol Moderates the Effects of Amyloid-β on Expression of HMG-CoA Reduct
7	2	29605487	2018	Association between ABCA1 gene polymorphisms and the therapeutic response to donepezil t
6	3	38699303	2024	Comparative gene regulatory networks modulating APOE expression in microglia and astrocy
6	3	37488092	2023	Inhibition of Sirt2 Decreases ApoE Secretion in Astrocytes and Microglial Cells.
6	3	30474860	2018	HDL mimetic peptides affect apolipoprotein E metabolism: equal supplement or functional
6	2	42554945	2026	GPR146 Deficiency Enhances Microglial Phagocytosis and Blood-Brain Barrier-Associated Ma
6	2	40661651	2025	Inhibition of Acyl-CoA: Cholesterol Acyltransferase 1 Promotes Shedding of Soluble TREM2
6	2	39612244	2024	Microglial APOE3 Christchurch protects neurons from Tau pathology in a human iPSC-based
6	2	38191520	2024	Sex-dependent effect of sublethal copper concentrations on de novo cholesterol synthesis
6	2	29323721	2018	Brain-derived neurotrophic factor modulates cholesterol homeostasis and Apolipoprotein E
4	4	39345217	2024	Deletion of miR-33, a regulator of the ABCA1-APOE pathway, ameliorates neuropathological
4	3	34949639	2021	Neuronal ROS-induced glial lipid droplet formation is altered by loss of Alzheimer's dis
4	3	29563219	2018	Small molecule inducers of ABCA1 and apoE that act through indirect activation of the LX
4	2	42325211	2026	Exploration of precision coregulator TR-FRET identifies diverse signatures for LXR ligan
4	2	41000830	2025	In search of nonlipogenic ABCA1 inducers (NLAI): precision coregulator TR-FRET identifie
4	2	31441725	2019	Integrated Genomic Analysis Revealed Associated Genes for Alzheimer's Disease in APOE4 N
4	2	31168344	2019	The effects of aerobic training before and after the induction of Alzheimer's disease on
3	3	34045954	2021	Dichlorodiphenyltrichloroethane Impairs Amyloid Beta Clearance by Decreasing Liver X Rec
3	2	42079117	2026	Epigenetically constrained astrocyte states underlie prefrontal cortex vulnerability in
3	2	40334811	2025	Astrocyte lactoferrin deficiency affects the construction and function of spinal neurons
3	2	39345559	2024	The mechanism and consequences of amyloid-β modulating thiamine pyrophosphokinase-1 expr
3	2	38856177	2024	Lysosomal cholesterol accumulation in aged astrocytes impairs cholesterol delivery to ne
3	2	36138870	2022	Application of Micro-Western Array for Identifying Different Serum Protein Expression Pr
3	2	33897406	2021	Interplay Between Microglia and Alzheimer's Disease-Focus on the Most Relevant Risks: AP
3	2	30010117	2018	ABCA7 Downregulation Modifies Cellular Cholesterol Homeostasis and Decreases Amyloid-β P

Extracted by k-dense from this queue: 39345217 (M1H2 + M3H1), 34949639 (M3H2). 37546938 was SKIPPED - it is the bioRxiv preprint of 38480892, already pooled.

Capture-recapture, and why I do not trust it

Treating each agent's search as a capture occasion: 292 distinct PMIDs, 167 singletons, 73 doubletons, Chao1 = 479 (95% CI 402-557), implying ~61% completeness. BUT leave-one-agent-out validation fails badly - holding out nakos predicts 310 missing papers and the agent actually contributed 43 unique. Median pairwise overlap is 0.51x of the independence expectation, so agents searched DIFFERENT niches and Chao1's homogeneity assumption is violated. The 61% figure is reported here only so nobody re-derives it and trusts it. Use the per-slice coverage table instead: it is measured, not modelled.