Characteristic developmental expression of amyloid beta40, 42 and 43 in patients with Down syndrome

Topic: Brain proteins, microglia and lab models

We immunohistochemically studied the expression of beta-amyloid precursor protein (APP), Abeta40, Abeta42, and Abeta43 in the frontal lobes of 20 Down syndrome (DS) patients and 13 controls. The immunoreactivity for each antibody was different in the degree of intensity and the chronological pattern of expression. APP and Abeta43 immunoreactivity was increased in neurons initially, and then Abeta43 and 42 immunoreactivity appeared in diffuse plaques from 32 years of age. APP and Abeta43 were characteristically observed in axons around senile plaques. Finally, Abeta40 immunoreactivity was detected in the cores of senile plaques. This time course of immunoreactive expression may be related to the pathogenetic process of Alzheimer-type dementia in DS, and the axonal damage in senile plaques may lead to the formation of neurofibrillary tangles (NFT) or neuronal death through axonal flow disturbance and accumulation of Abeta43 in cortical neurons.

@article{hirayama2003-12689696,
  author  = {Hirayama, A. and Horikoshi, Y. and Maeda, M. and Ito, M. and Takashima, S.},
  title   = {{Characteristic developmental expression of amyloid beta40, 42 and 43 in patients with Down syndrome}},
  journal = {Brain \& development},
  year    = {2003},
  doi     = {10.1016/s0387-7604(02)00209-7},
  pmid    = {12689696},
  url     = {https://doi.org/10.1016/s0387-7604(02)00209-7}
}

Key findings

• The immunoreactivity for each antibody was different in the degree of intensity and the chronological pattern of expression.
• APP and Abeta43 immunoreactivity was increased in neurons initially, and then Abeta43 and 42 immunoreactivity appeared in diffuse plaques from 32 years of age.
• APP and Abeta43 were characteristically observed in axons around senile plaques.
• Finally, Abeta40 immunoreactivity was detected in the cores of senile plaques.
• This time course of immunoreactive expression may be related to the pathogenetic process of Alzheimer-type dementia in DS, and the axonal damage in senile plaques may lead to the formation of neurofibrillary tangles (NFT) or neuronal death through axonal flow disturbance and accumulation of Abeta43 in cortical neurons.

Why it matters

This study describes the order in which different amyloid beta proteins appear in the brains of people with Down syndrome, with Abeta43 and 42 appearing in diffuse plaques from age 32. It suggests a time course related to Alzheimer-type dementia, but it does not test any treatment or cure.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/s0387-7604(02)00209-7
• PubMed: 12689696
• Original source →

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Studies this one cites

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

• 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
• Molecular mapping of Alzheimer-type dementia in Down's syndrome Annals of neurology · 1998-03-01 · usefulness score 54/100 · Risk genes beyond APOE
• Developmental and aging changes in the expression patterns of beta-amyloid in the brains of normal and Down syndrome cases Brain & development · 1990-01-01 · usefulness score 32/100 · Down syndrome and Alzheimer's

Later studies that cite this one

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

• A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome Nature reviews. Neuroscience · 2015-08-05 · usefulness score 52/100 · Risk factors
• Regulation of amyloid precursor protein processing by the Beclin 1 complex PloS one · 2010-06-15 · usefulness score 52/100 · Risk genes beyond APOE
• Dementia in Down's syndrome The Lancet. Neurology · 2016-04-11 · usefulness score 51/100 · Brain tissue and pathology
• Aging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology Current Alzheimer research · 2016-01-01 · usefulness score 47/100 · Inflammation and the immune system
• Alzheimer disease and Down syndrome: factors in pathogenesis Neurobiology of aging · 2005-03-01 · usefulness score 43/100 · Down syndrome and Alzheimer's
• Down syndrome, Alzheimer's disease and seizures Brain & development · 2005-06-01 · usefulness score 40/100 · Down syndrome and Alzheimer's

Related studies in Down syndrome and Alzheimer's

• Elevated expression of beta-site amyloid precursor protein cleaving enzyme 2 in brains of patients with Down syndrome Neuroscience letters · 2002-06-01 · usefulness score 38/100
• Developmental immunohistochemistry of growth inhibitory factor in normal brains and brains of patients with Down syndrome Pediatric neurology · 1997-09-01 · usefulness score 35/100
• STARD1 and NPC1 expression as pathological markers associated with astrogliosis in post-mortem brains from patients with Alzheimer's disease and Down syndrome Aging · 2020-01-05 · usefulness score 42/100
• High expression on Kunitz-type protease inhibitor-containing substances in the cerebral vessels of patients with Down syndrome The Tohoku journal of experimental medicine · 1994-11-01 · usefulness score 28/100
• Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome Proceedings of the National Academy of Sciences of the United States of America · 1996-11-01 · usefulness score 49/100
• SET translocation is associated with increase in caspase cleaved amyloid precursor protein in CA1 of Alzheimer and Down syndrome patients Neurobiology of aging · 2013-11-05 · usefulness score 39/100

Also tagged “down”

527 studies in the library carry the topic tag “down”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 527 tagged studies.

• Autoimmune thyroiditis associated with mild "subclinical" hypothyroidism in adults with Down syndrome: a comparison of patients with and without manifestations of Alzheimer disease American journal of medical genetics · 1990-06-01 · usefulness score 35/100 · Down syndrome and Alzheimer's
• Cholinesterase inhibitors: new roles and therapeutic alternatives Pharmacological research · 2004-10-01 · usefulness score 45/100 · Down syndrome and Alzheimer's
• The role of magnetic resonance imaging in the diagnosis of Alzheimer disease in adults with Down syndrome Archives of neurology · 1996-12-01 · usefulness score 35/100 · Down syndrome and Alzheimer's

Similar studies

• Beta-amyloid, oxidative stress and down syndrome 2006 · Down syndrome and Alzheimer's
• Increased amyloid beta protein levels in children and adolescents with Down syndrome 2007 · Down syndrome and Alzheimer's
• Reexpression of a developmentally regulated antigen in Down syndrome and Alzheimer disease 1988 · Down syndrome and Alzheimer's
• Sequence of Deposition of Heterogeneous Amyloid β-Peptides and APO E in Down Syndrome: Implications for Initial Events in Amyloid Plaque Formation 1996 · Down syndrome and Alzheimer's
• Development of Alzheimer disease in Down syndrome individuals 1983 · Down syndrome and Alzheimer's
• The Genetics and Mechanisms of Alzheimer's Disease in Down Syndrome 2026 · Down syndrome and Alzheimer's

More on Down syndrome and Alzheimer's

• A review that covers this ground Protein expression in Down syndrome brain Amino acids · 2001-12-01 · usefulness score 39/100
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• Newest in this subject Memory and Plasma pTau217 Refine Prognosis in Down Syndrome Annals of neurology · 2026-10-02 · Peer-reviewed · usefulness score 47/100

See all studies in Down syndrome and Alzheimer's →