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Table 2 Number of overlapping pathways and their overlap coefficient between the different Anle138b experiment pathway enrichment results (FDR-adjusted p-value ≤ 0.05), a summary of high-level processes described by the pathways and their relevance to AD

From: Mechanism of action deconvolution of the small-molecule pathological tau aggregation inhibitor Anle138b

Experiment 1

Experiment 2

Number of shared significant pathways (overlap coefficient)

Summary of processes

Relevance to AD

hAD Tau seeded RCNs, day 14

Unseeded RCNs, day 14

47 (0.59)

GPCR signalling

Extracellular matrix (ECM) organisation

Cholesterol homeostasis

Inflammation

Angiogenesis

Mediates both the inflammatory response in microglia and modulation of calcium signalling [26, 27]

Reduction in hippocampal ECM reverses memory deficits associated with AD [28]

Regulates both tau and amyloid pathology by independent mechanisms [29]

Causative of and aggravated by tau pathology [30]

Tau pathology induces blood vessel abnormalities [31]

hAD Tau seeded RCNs, day 7

Unseeded RCNs, day 7

4 (0.29)

Metabolism

Disruptions in metabolic processes linked to AD progression [32,33,34]

hAD Tau seeded RCNs, day 3

Unseeded RCNs, day 3

0 (0.00)

-

-