Case study · Life sciences

Which neurons Alzheimer’s disease takes first

Along the disease continuum, which cell types are lost earliest in the middle temporal gyrus?

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MantisReady2

Which neurons are lost earliest in Alzheimer’s disease, and where do they sit on this map?

I’ll read the donors and their pathology stages first, then compare cell-type proportions along the disease continuum.

Read space contextRunning(1s)›

get_space_context · SEA-AD brain

→ 80,000 nuclei · 24 types · 89 donors

Search this mapRunning(2s)›

search · semantic "somatostatin interneurons"

→ 3,412 matches, 91% in one cluster

Run commandRunning(5s)›

commandExecution · /bin/bash -lc "python proportions.py --by cps --types all"

→ # Cell-type proportions across pathology stages

proportions_by_stage.csv24 types · 4 stages

Sst interneurons fall first as pathology rises, ahead of most excitatory types. I’m outlining them and saving the early-stage donors as a bag.

Select regionRunning(1s)›

select · Sst · early pathology donors

→ 1,126 nuclei saved to Early Sst loss

Compare groupsRunning(2s)›

compare · low vs high pathology donors

→ 2 groups · 24 cell types

Somatostatin (Sst) interneurons are lost earliest 1, declining in the early phase of the disease continuum before the later loss of L2/3 IT excitatory neurons 23.Somatostatin (Sst) interneurons are lost earliest 1, declining in the early phase of the disease continuum before the later loss of L2/3 IT excitatory neurons 23.

Sources1Sst nucleus · early-pathology donor2L2/3 IT nucleus · late-pathology donor3Gabitto et al., Nat. Neurosci. 2024

Comparing groups/bin/bash -lc "python proportions.py…0:172

>Ask a follow-up, or point Mantis at a file…

AttachArtifacts/[+]31[m]Continuum-1

Every citation lights the exact records behind it

The Space

SEA-AD brain

80,000 nuclei from the middle temporal gyrus of 89 donors spanning the Alzheimer's disease continuum (SEA-AD), in 24 cell subclasses, with each donor's neuropathology, APOE4 status, cognition and pseudo-progression score.

Source: CZ CELLxGENE Discover, SEA-AD, Allen Institute (CC BY 4.0); Gabitto, Travaglini et al., Nature Neuroscience 27, 2366-2383 (2024).

80,000 records

Largest clusters in the map sample

L2/3 IT27%
L4 IT15%
L5 IT11%
Vip10%
Oligodendrocyte9%
Pvalb8%
Astrocyte6%
Sst6%

On the map

What to look for

Excitatory neurons (L2/3 IT, L4 IT, L5 IT) and inhibitory interneurons (Vip, Pvalb, Sst, Lamp5) form separate regions.
Glia (oligodendrocytes, astrocytes, microglia) sit apart from the neurons.
Each nucleus carries its donor’s neuropathology, APOE4 status and pseudo-progression score.

With Mantis

What to ask

Which cell subclasses decline as pseudo-progression rises?
Compare Sst interneurons between low and high pathology donors.
How do microglia differ by APOE4 status?

Ask in the Space

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