GRN-related Frontotemporal Lobar Degeneration TDP43 Type A presenting as a case of Posterior Cortical Atrophy (P5.013)

Abstract

OBJECTIVE: To expand the spectrum of clinical phenotypes associated with frontotemporal lobar degeneration (FTLD) pathology, describing to our knowledge the first case of a classical posterior cortical atrophy (PCA) syndrome. BACKGROUND: PCA is a clinicoradiologic syndrome characterized by progressive decline in visual processing skills with relatively intact memory in the early stages, and atrophy of posterior brain regions. It is generally regarded as a focal presentation of Alzheimer’s disease (AD) since most patients have amyloid plaques and neurofibrillary tangles, although less commonly Lewy Body pathology, corticobasal degeneration and even prion disease have been reported. DESIGN/METHODS: We describe the clinical and neuroimaging features of a case of PCA with surprising pathologic and genetic findings. RESULTS: A 63-year-old right-handed male presented with a 4-year history of insidious onset and progression of visual symptoms with mild word-finding difficulty and a right homonymous hemianopia evident on neurologic examination. A SPECT scan revealed asymmetric left occipitoparietal hypoperfusion. His father died of dementia in his 50s, clinically diagnosed as AD. The patient died 5 years after diagnosis and an autopsy confirmed FTLD with TDP-43 Type A inclusions (FTLD-TDP43A). Based on the pathologic findings, molecular genetic analysis was conducted and yielded a deletion in the progranulin (GRN) gene at exon 7, a known pathogenic mutation. CONCLUSIONS: Although it is well-known that GRN-related FTLD is associated with asymmetric parietal atrophy in addition to frontal and anterior temporal atrophy, we believe this is the first reported pathologically proven case of FTLD presenting as PCA.. It is interesting to speculate that as-yet-undiscovered genetic or other factors that may predispose to a posterior predominance of AD pathology in the most common form of PCA may also have been present in this patient, predisposing to TDP43A pathology with an occipitoparietal lobar degeneration topography. Supported by R21NS084156, R21NS077059, P50-AG005134

Disclosure: Dr. Mitchell has nothing to disclose. Dr. Lucente has nothing to disclose. Dr. Larvie has nothing to disclose. Dr. Frosch has received royalty payments from Elsevier. Dr. Dickerson has received personal compensation for activities with Pfizer, Inc., En Vivo, and Merck.