Human brain nascent polypeptide-associated complex alpha subunit is decreased in patients with Alzheimer' s disease and Down syndrome

Topic: Brain proteins, microglia and lab models

Nascent polypeptide-associated complex (NAC) protein, a heterodimeric complex of alpha- and beta-subunits, prevents mistargeting of nascent polypeptide chains to the endoplasmic reticulum membranes. alpha-NAC has sequence similarities with transcription-regulating proteins and has been reported to function as a transcriptional coactivator potentiating c-Jun-mediated transcription. Performing gene hunting using differential display-polymerase chain reaction, a downregulated sequence in the frontal cortex of patients with Alzheimer's disease (AD) and Down syndrome (DS) with AD-like neuropathology was identified as a-NAC with 100% homology. The significant decrease in alpha-NAC mRNA was shown by semiquantitative reverse transcription-polymerase chain reaction, and in parallel, the significant decrease of alpha-NAC protein, which was even more pronounced when related to either actin or neuron-specific enolase levels, was also observed in both disorders. Linear regression analysis revealed a strong, significant correlation between alpha-NAC protein and mRNA expression. In fetal DS brain, however, mRNA levels of alpha-NAC were comparable between DS and controls, suggesting that the decrease in alpha-NAC might be involved in the pathology of neurodegenerative diseases. The decrease in alpha-NAC as a transcriptional coactivator could contribute to the characteristic decline of the c-Jun-mediated transcriptional machinery and could function as the complementary mechanism in c-Jun-mediated apoptosis. Decreased alpha-NAC may result in the mistargeting, mistranslation, and proteolysis of proteins by affecting overall NAC function.

Key findings

• The significant decrease in alpha-NAC mRNA was shown by semiquantitative reverse transcription-polymerase chain reaction, and in parallel, the significant decrease of alpha-NAC protein, which was even more pronounced when related to either actin or neuron-specific enolase levels, was also observed in both disorders.
• Linear regression analysis revealed a strong, significant correlation between alpha-NAC protein and mRNA expression.
• In fetal DS brain, however, mRNA levels of alpha-NAC were comparable between DS and controls, suggesting that the decrease in alpha-NAC might be involved in the pathology of neurodegenerative diseases.
• Decreased alpha-NAC may result in the mistargeting, mistranslation, and proteolysis of proteins by affecting overall NAC function.

Why it matters

This study found reduced levels of a protein called alpha-NAC in the frontal cortex of people who had died with Alzheimer's disease and Down syndrome. It suggests this decrease may be involved in the disease process, but it does not test any treatment or show that raising this protein would help patients.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.2310/6650.2002.33287
• PubMed: 12109594
• 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{kim2002-12109594,
  author  = {Kim, S. H. and Shim, K. S. and Lubec, G.},
  title   = {{Human brain nascent polypeptide-associated complex alpha subunit is decreased in patients with Alzheimer' s disease and Down syndrome}},
  journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research},
  year    = {2002},
  doi     = {10.2310/6650.2002.33287},
  pmid    = {12109594},
  url     = {https://doi.org/10.2310/6650.2002.33287}
}

Related studies in Down syndrome and Alzheimer's

• Brain t-complex polypeptide 1 (TCP- 1) related to its natural substrate beta1 tubulin is decreased in Alzheimer's disease Life sciences · 2001-06-01 · usefulness score 37/100
• Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain Annals of neurology · 1983-01-01 · usefulness score 51/100
• Decreased cyclin dependent kinase in brain of patients with Down syndrome Neuroscience letters · 1996-09-01 · usefulness score 35/100
• Alpha-synuclein co-pathology in Down syndrome-associated Alzheimer's disease Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025-06-01 · usefulness score 54/100
• Drebrin, a dendritic spine protein, is manifold decreased in brains of patients with Alzheimer's disease and Down syndrome Neuroscience letters · 2002-05-01 · usefulness score 36/100
• Down syndrome, Alzheimer disease, and cerebral amyloid angiopathy: The complex triangle of brain amyloidosis Developmental neurobiology · 2019-07-01 · usefulness score 43/100

Similar studies

• 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
• Polyubiquitinylation Profile in Down Syndrome Brain Before and After the Development of Alzheimer Neuropathology 2017 · Down syndrome and Alzheimer's
• Synaptic actin stabilization protein loss in Down syndrome and Alzheimer disease 2020 · Down syndrome and Alzheimer's
• Neuronal apoptosis inhibitory protein (NAIP)-like immunoreactivity in brains of adult patients with Down syndrome 1999 · Down syndrome and Alzheimer's
• Alzheimer's disease and Down's syndrome: Sharing of a unique cerebrovascular amyloid fibril protein 1984 · Down syndrome and Alzheimer's
• Apoptosis-associated proteins p53 and APO-1/Fas (CD95) in brains of adult patients with Down syndrome 1999 · Down syndrome and Alzheimer's

More on Down syndrome and Alzheimer's

• A review that covers this ground Progressive worsening of adaptive functions in Down syndrome may be mediated by the complexing of soluble Abeta peptides with the alpha 7 nicotinic acetylcholine receptor: therapeutic implications Clinical neuropharmacology · 2003-09-01 · usefulness score 31/100
• 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 →