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Frontiers in Immunology

Immune protein has age-dependent effects in Alzheimer’s mice

Experiments in mice modeling Alzheimer’s disease found that dectin-1 reduced dense protein deposits at six months but impaired memory and learning at nine months.

Paper by Xi Wen, Ramona M. Rodriguiz, William C. Wetsel, Mari L. Shinohara · Duke University
Figure 1. Schematic of the Clec7aflox allele generation and the timeline of Clec7a deletion followed by mouse analysis.
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Figure 1. Schematic of the Clec7aflox allele generation and the timeline of Clec7a deletion followed by mouse analysis.Schematic of the Clec7aflox allele generation and the timeline of Clec7a deletion followed by mouse analysis.Xi et al.

Our read

Mechanisms
Studied:
Experiments in 5xFAD mice, against CKO mice
What changed:
Microglial dectin-1 reduced amyloid pathology in mid-life but worsened cognition and anxiety-related behavior in later life compared to CKO mice
The catch:
Synapses, neuronal circuits, and soluble amyloid-beta were not measured
Stake:
Ono Pharmaceutical funded the study.
In the record:
One of 18 papers on CLEC7A on record: none yet with results in people, 3 in animals.

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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In experiments with 5xFAD mice, a model of Alzheimer’s disease, researchers removed the protein dectin-1 from microglia, the brain’s resident immune cells. They triggered the genetic change at six to seven weeks of age and compared the mice with controls retaining dectin-1.

At six months, dectin-1 reduced dense amyloid-beta plaques, clumps of protein, in a brain region called the subiculum. Behavioral tests detected no difference. At nine months, dectin-1 impaired short-term memory and spatial learning. At 16 months, it increased freezing behavior, suggestive of heightened emotional reactivity.

Why it matters

The authors suggest that efforts to target dectin-1 to protect the brain during Alzheimer’s disease need to consider age, the cells carrying it and the molecules that activate it.

Caveats

The experiment removed dectin-1 early in life; it did not test a drug started later in the disease course. These results came from a mouse model, not people.

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