Background
Frontotemporal lobar degeneration is a neurodegenerative disease characterized by
brain atrophy of the frontal and anterior temporal lobes. The associated frontotemporal
dementia syndromes are clinically heterogeneous, and the pattern of affected cortical
regions varies among subtypes. The TMEM106B rs1990622 polymorphism is associated with frontotemporal lobar degeneration, but
little is known about how it affects the brain.
Methods
We investigated the rs1990622 polymorphism in relation to regional brain volumes to
identify potential structures through which TMEM106B confers risk for frontotemporal lobar degeneration. In 4413 nondemented and stroke-free
participants from the population-based Rotterdam Study, 150 cortical brain structures
and 6 commissural regions were segmented from magnetic resonance imaging.
Results
A distinct pattern of association was found between rs1990622 and gray matter volume
of left-sided temporal brain regions important for language processing, including
the superior temporal gyrus (β = −88.8 μL per risk allele, p = 7.64 × 10−5), which contains Wernicke’s area. The risk allele was also associated with a smaller
anterior commissure cross-sectional area (β = −.167 mm2 per risk allele, p = 4.90 × 10−5) and posterior part of the corpus callosum (β = −15.3 μL per risk allele, p = 1.23 × 10−5), both of which contain temporal lobe commissural tracts.
Conclusions
The asymmetric, predominantly left-sided involvement suggests an effect of TMEM106B on functions lateralized to the dominant hemisphere, such as language. These results
show that, in nondemented persons, TMEM106B influences the volume of temporal brain regions that are important for language processing.
Key Words
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Article info
Publication history
Published online: March 17, 2014
Accepted:
March 2,
2014
Received in revised form:
February 10,
2014
Received:
October 23,
2013
Identification
Copyright
© 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
