Objective: We present a case of corticobasal syndrome associated with a variant in the gene triggering receptor expressed on myeloid cells 2 (TREM2) and present the neuropathological findings.

Background: Corticobasal syndrome (CBS) is infrequently due to corticobasal degeneration when examined pathologically with many cases being due to Alzheimer’s disease (AD) or PSP pathology. TREM2 has a major role in regulating microglia and genome wide association studies suggest it may play a significant role in AD pathogeneis. In several European and North American populations TREM2 has been shown to increase the risk of developing Alzheimer’s Disease by 2-3 times.

Method: A 62-year-old right-handed male presented with word-finding difficulties. He stopped working aged 64. No family history of dementia. 2 years from onset speech was effortful with words mispronounced and phonemic paraphasias. His performance on the ACE-R showed cognitive impairment across all domains (63/100), most notably in tasks of attention, language, and memory. 6 years from onset he was effectively mute. He had left-side predominant paratonia and dystonic posturing. He died aged 69.

Results: MRI brain (at onset) showed mild involutional changes. FDG-PET CT (3 years from onset) was abnormal with severely decreased uptake in the right parietotemporal lobes, and mildly decreased uptake in the right frontal lobe. Moderate decreased uptake in the left parietotemporal lobes. Dementia NGS panel found he was heterozygous for the Arg47His variant in exon 2 of the TREM2 gene. DNA sequencing of exon 4 of the ApoE gene revealed ApoE3/E3 genotype. Histological examination of the brain showed advanced Alzheimer’s pathology. There was Lewy body pathology (diffuse neocortical, Braak stage 6), subcortical white matter pathology in the spectrum of age-related tau astrogliopathy, and moderate cerebral amyloid angiopathy. No TDP43 pathology was identified.

Conclusion: This patient’s phenotype began as a non-fluent agrammatic progressive aphasia with evolving findings supportive of corticobasal syndrome. Initially we felt this was possibly due to language variant frontotemporal dementia. On reflection, the spread of cognitive domains affected was more suggestive of AD pathology. TREM2 may be something to keep in mind in dementia cases when the cognitive profile is typical of AD but the patients are younger and disease progression is more rapid.

References: Presented virtually at the IICN Registrar’s Prize in Clinical Neurosciences, Dublin 2021

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MDS Abstracts - https://www.mdsabstracts.org/abstract/yet-another-cause-of-corticobasal-syndrome-a-case-of-trem2-related-alzheimers-disease-presenting-as-corticobasal-syndrome/