Objective:

To examine the relationship between obsessive-compulsive symptoms and caudate tau pathology in behavioral variant frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA) due to frontotemporal lobar degeneration with tau pathology (FTLD-tau).

Background:

Dysfunction in the caudate nucleus, a region involved in regulating, initiating, and inhibiting actions, has been implicated in obsessive-compulsive disorder and FTLD. Behavioral changes, including ritualistic and compulsive behaviors, are common in bvFTD and PPA and are distressing for caregivers, representing targets for intervention.

Design/Methods:

We identified 58 right-handed participants with autopsy-confirmed FTLD-tau from the Northwestern Alzheimer’s Disease Research Center (NU-ADRC) brain bank (bvFTD: n = 21; PPA: n = 37; 3R tau: n = 27; 4R tau: n = 31). Participants completed annual research visits through the NU-ADRC PPA Research Program or clinical core using the NACC Uniform Data Set or FTLD-Module. OCD-like symptoms were classified by consensus review of clinical data and medical records. The head of the left caudate nucleus was sectioned from 13 participants (3R tau: n=6, 4R tau: n=7). Sections were immunostained with AT8 to detect phosphorylated tau, and percent AT8-positive area was quantified in QuPath. Fisher’s exact tests compared OCD prevalence between 3R and 4R tau groups. We assessed the association between dementia diagnosis, tau species, and OCD status and caudate AT-8 burden via mixed-effects linear regression.

Results:

OCD-like symptoms were more frequent in 3R (52%) than 4R tauopathies (23%) (p<0.05). Caudate AT-8 % area trended higher in 3R (M=15.81%) than 4R tau cases (M=7.25%, p=0.052) but did not vary substantially by OCD status or dementia syndrome.

Conclusions:

Preliminary findings suggest a link between OCD features and 3R vs. 4R tau burden in the caudate. Future analyses will assess pathologic burden in additional striatal regions to better understand the biological substrates of ritualistic and compulsive behaviors in this population.