Defined neurofilament, tau, and beta-amyloid precursor protein epitopes distinguish Alzheimer from non-Alzheimer senile plaques

Topic: Amyloid, tau and blood-test diagnosis

Eight antisera and one monoclonal antibody to synthetic peptides that corresponded to domains extending over the entire length of the beta-amyloid precursor protein (beta-APP), and an antiserum to the full-length 695-amino acid form of the beta-APP, were raised to probe the composition of the core and corona of senile plaques (SPs). We localized distinct beta-APP domains, including the beta-amyloid protein or A4 region, within the SPs of 13 end-stage Alzheimer disease (AD) and 13 age-matched control samples of hippocampus and entorhinal cortex. The composition of SPs also was probed with antibodies to defined epitopes in tau (tau) as well as the large and mid-size neurofilament (NF) proteins.

Key findings

• We localized distinct beta-APP domains, including the beta-amyloid protein or A4 region, within the SPs of 13 end-stage Alzheimer disease (AD) and 13 age-matched control samples of hippocampus and entorhinal cortex.
• The composition of SPs also was probed with antibodies to defined epitopes in tau (tau) as well as the large and mid-size neurofilament (NF) proteins.
• The most important observations were that beta-APP domains outside the A4 region were largely restricted to SP coronas in the AD samples, together with tau and NF determinants, whereas the same epitopes were absent from A4-positive blood vessels and exceptionally rare in non-AD SPs.
• Indeed, samples from a subset of the non-AD cases contained a considerable number of A4-positive SPs totally devoid of any of the other beta-APP, tau, and NF epitopes.

Why it matters

Using antibodies to defined epitopes, this study found that beta-amyloid precursor protein domains outside the A4 region were largely restricted to senile plaque coronas in Alzheimer samples. It is a descriptive tissue study and does not test any treatment, cure or prevention.

New to this subject? Start with our plain-English guide: Genetics →

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1073/pnas.87.6.2249
• PubMed: 1690426
• Original source →
• Free full text: PubMed Central →

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

@article{arai1990-1690426,
  author  = {Arai, H. and Lee, V. M. and Otvos, L. and Greenberg, B. D. and Lowery, D. E. and Sharma, S. K. and Schmidt, M. L. and Trojanowski, J. Q.},
  title   = {{Defined neurofilament, tau, and beta-amyloid precursor protein epitopes distinguish Alzheimer from non-Alzheimer senile plaques}},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year    = {1990},
  doi     = {10.1073/pnas.87.6.2249},
  pmid    = {1690426},
  url     = {https://doi.org/10.1073/pnas.87.6.2249}
}

Studies this one cites

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

• Diagnosis of Alzheimer's Disease Archives of Neurology · 1985-11-01 · usefulness score 58/100 · Getting a diagnosis
• The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor Nature · 1987-02-01 · usefulness score 58/100 · Disease mechanisms
• Amyloid plaque core protein in Alzheimer disease and Down syndrome Proceedings of the National Academy of Sciences of the United States of America · 1985-06-01 · usefulness score 56/100 · Down syndrome and Alzheimer's
• Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein Biochemical and Biophysical Research Communications · 1984-05-01 · usefulness score 54/100 · Disease mechanisms
• Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues Proceedings of the National Academy of Sciences of the United States of America · 1988-10-01 · usefulness score 49/100 · Risk genes beyond APOE
• The immunohistochemical demonstration of subsequences of the precursor of the amyloid A4 protein in senile plaques in Alzheimer's disease Neuropathology and applied neurobiology · 1989-03-01 · usefulness score 36/100 · Biomarkers

Later studies that cite this one

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

• Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein Nature · 1995-02-01 · usefulness score 59/100 · Risk genes beyond APOE
• Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene Nature genetics · 1992-06-01 · usefulness score 58/100 · Brain tissue and pathology
• Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease Proceedings of the National Academy of Sciences of the United States of America · 1994-09-01 · usefulness score 45/100 · Genetics
• Morphological and biochemical analyses of amyloid plaque core proteins purified from Alzheimer disease brain tissue Journal of neurochemistry · 1993-11-01 · usefulness score 44/100 · Risk genes beyond APOE
• Intracellular amyloid and the neuronal origin of Alzheimer neuritic plaques Neurobiology of disease · 2014-08-01 · usefulness score 43/100 · Risk genes beyond APOE
• Secreted beta-amyloid precursor protein stimulates mitogen-activated protein kinase and enhances tau phosphorylation Proceedings of the National Academy of Sciences of the United States of America · 1994-07-01 · usefulness score 42/100 · Risk genes beyond APOE

Related studies in Risk genes beyond APOE

• Accumulation of amyloid beta and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig Journal of neuropathology and experimental neurology · 1999-09-01 · usefulness score 46/100
• Secreted amyloid β–protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease Nature Medicine · 1996-08-01 · usefulness score 59/100
• Copper inhibits beta-amyloid production and stimulates the non-amyloidogenic pathway of amyloid-precursor-protein secretion The Biochemical journal · 1999-12-01 · usefulness score 41/100
• Non-fibrillar beta-amyloid protein is associated with smooth muscle cells of vessel walls in Alzheimer disease Journal of neuropathology and experimental neurology · 1994-11-01 · usefulness score 40/100
• Calcium-mediated transient phosphorylation of tau and amyloid precursor protein followed by intraneuronal amyloid-beta accumulation The Journal of biological chemistry · 2006-11-03 · usefulness score 41/100
• Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein Proceedings of the National Academy of Sciences of the United States of America · 1991-09-01 · usefulness score 48/100

Also tagged “phosphorylated”

732 studies in the library carry the topic tag “phosphorylated”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 732 tagged studies.

• Sleep Deprivation Affects Tau Phosphorylation in Human Cerebrospinal Fluid Annals of neurology · 2020-02-27 · usefulness score 63/100 · Disease mechanisms
• Comparison of Plasma Phosphorylated Tau Species With Amyloid and Tau Positron Emission Tomography, Neurodegeneration, Vascular Pathology, and Cognitive Outcomes JAMA neurology · 2021-09-01 · usefulness score 65/100 · Biomarkers
• Association of elevated phospho-tau levels with Alzheimer-typical 18F-fluoro-2-deoxy-D-glucose positron emission tomography findings in patients with mild cognitive impairment Biological psychiatry · 2004-08-01 · usefulness score 42/100 · Tau biomarkers

Similar studies

• Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study 2004 · Getting a diagnosis
• The amyloid precursor protein of Alzheimer's disease is released by human platelets 1990 · Risk genes beyond APOE
• Amyloid precursor protein revisited: neuron-specific expression and highly stable nature of soluble derivatives 2012 · Risk genes beyond APOE
• The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer disease subjects 1989 · Risk genes beyond APOE
• The Alzheimer amyloid precursor protein. Identification of a stable intermediate in the biosynthetic/degradative pathway 1990 · Risk genes beyond APOE
• β-Amyloid, Tau, Neurodegeneration Classification and Eligibility for Anti-amyloid Treatment in a Memory Clinic Population 2022 · Drug development

More on Risk genes beyond APOE

• A review that covers this ground The pathogenesis of senile plaques Journal of neuropathology and experimental neurology · 1997-04-01 · usefulness score 50/100
• Newest in this subject Pregnancy History and Loss of Normal PSEN2 Function Impact Female Late-Life Cognitive Processing, Inhibitory Signaling, and Gliosis bioRxiv · 2026-10-30 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Temporal Proteomics Links the APP London Mutation to Early Cholesterol Remodeling Cell Programs in Human Neurons bioRxiv · 2026-10-24 · Preprint — not yet peer-reviewed · usefulness score 16/100

See all studies in Risk genes beyond APOE →