Immune-mediated platelet depletion augments Alzheimer's disease in mice: Study

A new research paper titled "Immune-mediated platelet depletion augments Alzheimer's disease neuropathological hallmarks in APP-PS1 mice" has been published in the journal Aging.

In Alzheimer's disease (AD), platelets become dysfunctional and could contribute to amyloid beta deposition. In a recent study, researchers from Paracelsus Medical University and the Austrian Cluster for Tissue Regeneration in Austria depleted platelets in one-year-old APP Swedish PS1 dE9 (APP-PS1) transgenic mice for five days, using intraperitoneal injections of an anti-CD42b antibody, and assessed changes in cerebral amyloidosis, plaque-associated neuritic dystrophy and gliosis.

The researchers explain, "The potential role of platelets in amyloid beta deposition led to the hypothesis that reducing platelet numbers might ameliorate AD pathology [30]. Here, we performed immune-mediated platelet depletion in APP-PS1 mice with an already fully developed amyloidosis and investigated its effects on classical hallmarks of AD: amyloid plaque pathology, plaque-associated neuritic dystrophy and gliosis."

In APP-PS1 female mice, platelet depletion shifted amyloid plaque size distribution towards bigger plaques and increased neuritic dystrophy in the hippocampus. In platelet-depleted females, plaque-associated Iba1+ microglia had lower amounts of fibrillar amyloid beta cargo and GFAP+ astrocytic processes showed a higher overlap with thioflavin S+ amyloid plaques.

In contrast to the popular hypothesis that platelets foster plaque pathology, data from this study suggest that platelets might limit plaque growth and attenuate plaque-related neuritic dystrophy at advanced stages of amyloid plaque pathology in APP-PS1 female mice. Whether the changes in amyloid plaque pathology are due to a direct effect on amyloid beta deposition or are a consequence of altered glial function must be further elucidated.

"In APP-PS1 females, acute thrombocytopenia aggravates AD neuropathology, suggesting that platelets might have a protective function in AD. However, the underlying molecular mechanisms by which platelets modulate amyloid plaque deposition remain elusive and need to be investigated in future experiments," the researchers conclude.