Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Jan;2(1):632-7.
doi: 10.1159/000345980. Epub 2012 Dec 15.

Association of BACE1 Gene Polymorphism with Cerebellar Volume but Not Cognitive Function in Normal Individuals

Alex Tsai  1 , Chu-Chung Huang, Albert C Yang, Mu-En Liu, Pei-Chi Tu, Chen-Jee Hong, Ying-Jay Liou, Jin-Fan Chen, Ching-Po Lin, Shih-Jen Tsai
Affiliations

Association of BACE1 Gene Polymorphism with Cerebellar Volume but Not Cognitive Function in Normal Individuals

Alex Tsai et al. Dement Geriatr Cogn Dis Extra. 2012 Jan.

Abstract

Aims: β-Site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a biological and positional candidate gene for Alzheimer's disease (AD). Previous studies found that BACE1-null mice had impaired performance on cognition and neurodegeneration during the aging process. Additionally, a synonymous polymorphism of BACE1 (rs638405) in exon 5 has been reported to be associated with risk for AD. We hypothesized that this BACE1 gene variant might influence regional brain volumes and cognitive tests in normal individuals.

Methods: Participants were 330 normal volunteers between 21 and 92 years of age (mean age 56.3 ± 22.0 years; 191 males, 139 females). Cognitive tests (the Mini-Mental State Examination and Digit Spans), magnetic resonance imaging, and genotyping of BACE1 rs638405 were examined for each subject. The differences in regional gray matter (GM) volumes between G homozygotes and C-allele carriers were tested using optimized voxel-based morphometry.

Results: Compared to C-allele carriers, G homozygotes exhibited significantly larger GM volumes in the left cerebellar culmen and right cerebellar lingual area, but no significant differences on cognitive function tests.

Conclusion: The findings suggest that the BACE1 rs638405 polymorphism may affect cerebellar morphology, but not cognitive function in healthy humans.

Keywords: Cerebellum; Cognition; Polymorphism; Volumetry; β-Site amyloid precursor protein-cleaving enzyme 1.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Regions showing significant GM volume reduction in C-carriers of BACE1 genotype compared with GG homozygotes. a Regions showing larger regional GM volume in GG homozygotes than C-carriers in the left cerebellar culmen and right cerebellar lingual area. b The glass brain map showing the spatial distribution of GM reduction in subjects with C allele of BACE1 (statistical criteria: uncorrected p < 0.001 with cluster size = 503 voxels). No area of regional GM volume reduction was found in GG homozygotes. Rt = Right; Lt = left.
See this image and copyright information in PMC

References

    1. Sinha S, Lieberburg I. Cellular mechanisms of beta-amyloid production and secretion. Proc Natl Acad Sci USA. 1999;96:11049–11053. - PMC - PubMed
    1. Cole SL, Vassar R. The basic biology of BACE1: a key therapeutic target for Alzheimer's disease. Curr Genomics. 2007;8:509–530. - PMC - PubMed
    1. Pastorino L, Ikin AF, Lamprianou S, Vacaresse N, Revelli JP, Platt K, Paganetti P, Mathews PM, Harroch S, Buxbaum JD. BACE (beta-secretase) modulates the processing of APLP2 in vivo. Mol Cell Neurosci. 2004;25:642–649. - PubMed
    1. Laird FM, Cai H, Savonenko AV, Farah MH, He K, Melnikova T, Wen H, Chiang HC, Xu G, Koliatsos VE, Borchelt DR, Price DL, Lee HK, Wong PC. BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. J Neurosci. 2005;25:11693–11709. - PMC - PubMed
    1. Blacker D, Bertram L, Saunders AJ, Moscarillo TJ, Albert MS, Wiener H, Perry RT, Collins JS, Harrell LE, Go RC, Mahoney A, Beaty T, Fallin MD, Avramopoulos D, Chase GA, Folstein MF, McInnis MG, Bassett SS, Doheny KJ, Pugh EW, Tanzi RE, NIMH Genetics Initiative Alzheimer's Disease Study Group Results of a high-resolution genome screen of 437 Alzheimer's disease families. Hum Mol Genet. 2003;12:23–32. - PubMed