Activated Alzheimer disease platelets retain more beta amyloid precursor protein

Topic: Amyloid, tau and blood-test diagnosis

Upon activation, platelet alpha-granules' soluble contents are secreted and membrane-bound contents are translocated to the plasma membrane. Membrane-bound proteins include the beta-amyloid precursor protein (APP) from which the beta-amyloid (A beta) deposits found surrounding the cerebrovasculature of patients with Alzheimer's Disease (AD) may originate. We show here that activated platelets from AD patients exhibit less APP processing, retain more of the protein on their surface, and secrete less as soluble fragments than do controls. Surface labeling demonstrated that there is little APP or CD62 on the surface of resting platelets. Upon activation, control platelets exhibited more of both proteins on their surface, while advanced AD patients exhibited similar amounts of CD62 as controls, but retained significantly more surface APP. AD platelets secreted similar amounts of most soluble alpha-granule contents as controls, but less APP fragments. Together these results suggest a processing defect that may account for greater deposition of A beta-containing products in the vasculature to which activated platelets adhere.

@article{davies1997-9258891,
  author  = {Davies, T. A. and Long, H. J. and Sgro, K. and Rathbun, W. H. and McMenamin, M. E. and Seetoo, K. and Tibbles, H. and Billingslea, A. M. and others},
  title   = {{Activated Alzheimer disease platelets retain more beta amyloid precursor protein}},
  journal = {Neurobiology of aging},
  year    = {1997},
  doi     = {10.1016/s0197-4580(97)00013-4},
  pmid    = {9258891},
  url     = {https://doi.org/10.1016/s0197-4580(97)00013-4}
}

Key findings

• Surface labeling demonstrated that there is little APP or CD62 on the surface of resting platelets.
• Upon activation, control platelets exhibited more of both proteins on their surface, while advanced AD patients exhibited similar amounts of CD62 as controls, but retained significantly more surface APP.
• Together these results suggest a processing defect that may account for greater deposition of A beta-containing products in the vasculature to which activated platelets adhere.

Why it matters

When blood platelets from people with Alzheimer's were activated, they processed less amyloid precursor protein, kept more of it on their surface and released fewer of its fragments than platelets from controls. The authors suggest this processing defect may help explain the greater buildup of amyloid-beta in blood vessels where activated platelets stick. It is a mechanism finding that does not test any treatment.

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Study details

• Study designclinical trial
• Evidence strengthLow

Read the original

• DOI: 10.1016/s0197-4580(97)00013-4
• PubMed: 9258891
• Original source →
• Free full text: Neurobiology of Aging →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• The amyloid precursor protein of Alzheimer's disease is released by human platelets The Journal of biological chemistry · 1990-09-01 · usefulness score 47/100 · Risk genes beyond APOE

Later studies that cite this one

3 studies in the alzhub library list this one in their references.

• [alpha]-Secretase ADAM10 as well as [alpha]APPs is reduced in platelets and CSF of Alzheimer disease patients Molecular medicine (Cambridge, Mass.) · 2002-02-01 · usefulness score 44/100 · Risk genes beyond APOE
• Amyloid precursor protein in platelets of patients with Alzheimer disease: effect of acetylcholinesterase inhibitor treatment Archives of neurology · 2001-03-01 · usefulness score 44/100 · Risk genes beyond APOE
• Alzheimer disease and platelets: how's that relevant Immunity & ageing : I & A · 2012-09-17 · usefulness score 42/100 · Risk genes beyond APOE

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• Altered amyloid protein processing in platelets of patients with Alzheimer disease Archives of neurology · 1997-02-01 · usefulness score 45/100
• Amyloid beta peptide potentiates cytokine secretion by interleukin-1 beta-activated human astrocytoma cells Proceedings of the National Academy of Sciences of the United States of America · 1995-11-01 · usefulness score 41/100

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