Elevated expression of beta-site amyloid precursor protein cleaving enzyme 2 in brains of patients with Down syndrome

Topic: Brain proteins, microglia and lab models

The gene encoding the beta-site amyloid precursor protein cleaving enzyme 2 (BACE2) has been determined to be located on the long arm of chromosome 21 at 21q22.3. BACE2 cleaves the amyloid precursor protein at the beta-secretase site and is thought to contribute to amyloid beta protein production. In the present study, changes in the expression of BACE2 were investigated immunohistochemically in the frontal cortex of patients with Down syndrome (DS). The immunoreactivity for BACE2 was detected in neurofibrillary tangle-bearing neurons from the elderly DS brains with Alzheimer-type neuropathology, but were not detected in those of DS brains without Alzheimer-type neuropathology or of control brains of any age. This suggests the possibility that the elevated expression of BACE2 is involved in the Alzheimer-type neuropathology of DS.

Key findings

• The gene encoding the beta-site amyloid precursor protein cleaving enzyme 2 (BACE2) has been determined to be located on the long arm of chromosome 21 at 21q22.3.
• BACE2 cleaves the amyloid precursor protein at the beta-secretase site and is thought to contribute to amyloid beta protein production.
• In the present study, changes in the expression of BACE2 were investigated immunohistochemically in the frontal cortex of patients with Down syndrome (DS).
• The immunoreactivity for BACE2 was detected in neurofibrillary tangle-bearing neurons from the elderly DS brains with Alzheimer-type neuropathology, but were not detected in those of DS brains without Alzheimer-type neuropathology or of control brains of any age.
• This suggests the possibility that the elevated expression of BACE2 is involved in the Alzheimer-type neuropathology of DS.

Why it matters

This study found that BACE2 immunoreactivity was detected in neurons with neurofibrillary tangles in elderly Down syndrome brains with Alzheimer-type pathology, but not in those without. It suggests a possible involvement of BACE2, but it does not test any treatment or prevention.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/s0304-3940(02)00287-2
• PubMed: 12052539
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{motonaga2002-12052539,
  author  = {Motonaga, K. and Itoh, M. and Becker, L. E. and Goto, Y. and Takashima, S.},
  title   = {{Elevated expression of beta-site amyloid precursor protein cleaving enzyme 2 in brains of patients with Down syndrome}},
  journal = {Neuroscience letters},
  year    = {2002},
  doi     = {10.1016/s0304-3940(02)00287-2},
  pmid    = {12052539},
  url     = {https://doi.org/10.1016/s0304-3940(02)00287-2}
}

Studies this one cites

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

• Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome Annals of Neurology · 1985-03-01 · usefulness score 56/100 · Down syndrome and Alzheimer's
• 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
• A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase Cytogenetics and cell genetics · 2000-01-01 · usefulness score 35/100 · Down syndrome and Alzheimer's

Later studies that cite this one

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

• Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice The Journal of biological chemistry · 2005-06-29 · usefulness score 50/100 · Down syndrome and Alzheimer's
• 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
• Down syndrome, Alzheimer's disease and seizures Brain & development · 2005-06-01 · usefulness score 40/100 · Down syndrome and Alzheimer's
• Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2 Genes, brain, and behavior · 2009-09-22 · usefulness score 34/100 · Down syndrome and Alzheimer's

Related studies in Down syndrome and Alzheimer's

• Chronic elevation of S100 beta protein does not alter APP mRNA expression or promote beta-amyloid deposition in the brains of aging transgenic mice Brain research · 1995-12-01 · usefulness score 33/100
• Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients Science (New York, N.Y.) · 1998-01-01 · usefulness score 41/100
• 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
• 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
• Mapping of the gene encoding the beta-amyloid precursor protein and its relationship to the Down syndrome region of chromosome 21 Proceedings of the National Academy of Sciences of the United States of America · 1988-11-01 · usefulness score 44/100
• Promoter mutations that increase amyloid precursor-protein expression are associated with Alzheimer disease American journal of human genetics · 2006-04-10 · usefulness score 47/100

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.

• Radioresistant DNA synthesis and human genetic diseases Human genetics · 1989-05-01 · usefulness score 35/100 · Down syndrome and Alzheimer's
• Hypersensitivity to ionizing radiation in cultured cells from Down syndrome patients Journal of the neurological sciences · 1985-05-01 · usefulness score 35/100 · Down syndrome and Alzheimer's
• Oxidative stress and mitochondrial dysfunction in Down syndrome Advances in experimental medicine and biology · 2012-01-01 · usefulness score 41/100 · Down syndrome and Alzheimer's

Similar studies

• Expression of the amyloid precursor protein gene in mouse oocytes and embryos 1991 · Down syndrome and Alzheimer's
• Increased amyloid beta protein levels in children and adolescents with Down syndrome 2007 · Down syndrome and Alzheimer's
• Protein expression in Down syndrome brain 2001 · Down syndrome and Alzheimer's
• Elimination of amyloid precursor protein in senile plaques in the brain of a patient with Alzheimer-type dementia and Down syndrome 2019 · Down syndrome and Alzheimer's
• Differential processing of amyloid-beta precursor protein directs human embryonic stem cell proliferation and differentiation into neuronal precursor cells 2009 · Down syndrome and Alzheimer's
• Characteristic developmental expression of amyloid beta40, 42 and 43 in patients with Down syndrome 2003 · Down syndrome and Alzheimer's

More on Down syndrome and Alzheimer's

• A review that covers this ground beta-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer's disease Trends in neurosciences · 1993-10-01 · usefulness score 36/100
• Newest in this subject Differential endothelial cell remodeling in Down syndrome and APP duplication drives distinct blood brain barrier dysfunction bioRxiv · 2026-10-30 · Preprint — not yet peer-reviewed · usefulness score 16/100
• 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 →