ALZHEIMER’S · INSIGHT

Shared gene links. What do they tell us?

22,283 probes · 31 people

The question

In brain tissue (hippocampus) from 31 people, we looked for genes whose expression follows the same pattern as one of two anchor genes, PLD2 or TPP2, at every stage of Alzheimer’s disease. Are these gene links specific to the disease?

The finding

Across PLD2 and TPP2, 13 of 16 stable links are also stable in the control group, people without Alzheimer’s (PLD2: 12 of 14). So a link that recurs in every disease stage is not necessarily specific to the disease.

Explore the recurring gene links

PLD2 · 45 recurring candidates

DRAG TO PAN · CLICK A PROBE

AnchorCandidate: in the anchor’s cluster in all three stagesIn the anchor’s cluster at this stage only

Click a probe on the map to see its gene and whether it is a candidate.

Each dot is one probe. For each disease stage, t-SNE arranges the probes so that those with similar expression patterns across that stage’s people sit close together, and K-Means cuts the map into 35 clusters. Candidates share the anchor’s cluster on all three stage maps. Switch stages to see the same candidates on each stage’s own map.

Check one link in all four groups

Pick a blue candidate on the map, or choose one below.

Choose a candidate

PTPN1

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Correlation with PLD2, group by group

Each bar is the Pearson correlation between this probe and the anchor across the people in one group: +1 means their expression rises and falls together. The thin line spans the correlations obtained when each person in the group is left out in turn.

0 of 54 candidates are associated with cognition or tangle pathology after correction for multiple testing.

01Do these links also occur without Alzheimer’s?Candidates → stable links → also stable in controls

Also stable in controls Not stable in controls

A link is “stable” when its correlation with the anchor stays positive however the group is resampled by leaving out one person at a time (22 recalculations across the three disease stages; 9 in the control group). Each mark is one stable link: click it to show that candidate on the map and in “Check one link in all four groups”.

02Are the candidates associated with disease?54 candidates vs. all 22,283 probes

For every probe we tested whether its expression tracks cognition (MMSE, a cognitive test score) or pathology (NFT, neurofibrillary tangles) across the 31 people, adjusting for age, sex and post-mortem interval. q is the p-value after Benjamini–Hochberg correction across 44,566 tests (22,283 probes × 2 measures); a probe passes when q < 0.05.