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Immunolocalisation of beta-amyloid precursor protein to plaque-associated synaptic alterations in the early and late stages of Alzheimer's disease

journal contribution
posted on 2023-05-16, 11:22 authored by Saunders, HL, Tracey DicksonTracey Dickson, James VickersJames Vickers
Extracellular deposition of insoluble β-amyloid protein into plaque-like structures is a key pathological feature of Alzheimer's disease (AD). A fundamental issue is the origin of the β-amyloid that comprises plaques and how this relates to the neuronal and synaptic alterations associated with this disease. Multiple labelling immunohistochemistry was utilised to localise β-amyloid precursor protein (APP), relative to β-amyloid, synaptic proteins and markers for the staging of cytoskeletal changes underlying neurofibrillary pathology. Clusters of APP labelled globular structures were present in a subset (3-45%) of neocortical β-amyloid plaques in both AD and preclinical AD cases. A higher proportion of plaques in layers V and VI were associated with APP labelled pathological structures than plaques in layers II and III. In contrast, virtually no plaques in layer I were associated with APP labelled structures. Double labelling verified that the clusters of APP immunoreactive elements did not occur in the absence of β-amyloid deposits. Furthermore, the APP labelled globular structures were localised to a subset of neuritic plaques. At a cellular level, APP immunoreactivity colocalised with a synaptic marker, chromogranin A, but not with the neuritic abnormalities labelled with antibodies to neurofilaments or tau. These data indicate that the clusters of APP immunoreactive material are unlikely to contribute towards the β-amyloid misprocessing that leads to the development of plaques in AD. Alternatively, APP labelling may be a marker for reactive synaptogenesis, possibly in response to the neuritic damage caused by plaque formation. © MSJ.


Publication title

Alzheimer's Reports






Tasmanian School of Medicine


Cardiff University School of Biosciences

Place of publication

United Kingdom

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  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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