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Cell Reports

Gene change reduced dementia-linked protein clumps in mice

Experiments in genetically engineered mice found that the Christchurch mutation reduced some protein clumps associated with Alzheimer’s disease and other dementias.

Paper by Carlos M. Soto-Faguás, Abigail O’Niel, Elizabeth Saltonstall, +5 more authorsVivek K. Unni
Graphical abstract from Cell Reports
Open the figure at full size
Graphical abstract. Soto-Faguás et al., CC BY-NC

Our read

Mechanisms
Studied:
Experiments in mice with the APOE Christchurch mutation, against APOE WT mice
What changed:
Mice with the Christchurch mutation had less formation and spread of alpha-synuclein clumps than mice with unaltered APOE
The catch:
The mutation did not reduce amyloid or tau abnormalities in models without brain injections

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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Mice with the Christchurch mutation engineered into their own APOE gene underwent experiments tracking dementia-linked protein buildup. APOE provides instructions for a protein that transports fats. In an Alzheimer’s mouse model, the mutation reduced amyloid-beta buildup and amyloid-triggered tau abnormalities after researchers injected Alzheimer’s-related tau into the brain. Amyloid-beta and tau are proteins linked to Alzheimer’s disease. The mutation did not change either protein’s abnormalities in separate genetically engineered mouse models without those injections.

The mutation also reduced the formation and spread of alpha-synuclein clumps in the brain. This protein is linked to Parkinson’s disease and dementia with Lewy bodies. The altered APOE protein bound more strongly to alpha-synuclein than the unaltered version did. Mice carrying the mutation also had higher blood cholesterol and triglycerides, another type of fat.

Why it matters

Age-related brain diseases involve several kinds of protein buildup. These experiments address whether APOE’s effects extend beyond the proteins most closely associated with Alzheimer’s disease.

Caveats

The experiments tested a mutation in mice’s own APOE gene, leaving open whether it would have the same effects in people.

Where the evidence stands

APOE

Cells, mice and humans: replicated by independent labs. Worms or flies: a single group.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 302 independent labs in 53 countries
  • 124 findings against
  • Funders: National Institute on Aging and others
  • 200 of 1,430 findings with company ties

APP

Mice: replicated by independent labs. Cells, worms or flies and humans: a single group.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

No results posted: trials that ended over a year ago with no results on ClinicalTrials.gov and no paper reporting them.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 89 independent labs in 24 countries
  • 4 findings against
  • 57 trials, 9 with no results posted
  • Funders: National Institute on Aging and others
  • 31 of 208 findings with company ties
  • 56 of 57 trials sponsored by developers of drugs aimed at it

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