Abstract Details

Title Clinicopathological Characteristics of Frontotemporal Dementia with Parkinsonism Linked to the N279K Mutation

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P3 - Poster Session 3 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-005

Objective To compare the clinicopathological characteristics of largest clinically and pathologically studied kindred with MAPT N279K mutation, known as the pallidopontonigral degeneration (PPND), with progressive supranuclear palsy (PSP) patients.

Background

Mutations in the MAPT gene can lead to inherited forms of frontotemporal dementia with parkinsonism. The N279K mutation alters the normal 3-repeat/4-repeat isoform ratio of tau, favoring the aggregation-prone 4-repeat isoform.

Design/Methods This study includes 17 patients from the PPND Family, 18 patients with early-onset PSP (EPSP), and 19 patients with classical-onset PSP (CPSP). Diagnosis was confirmed through postmortem pathological examination. We performed a retrospective analysis of clinical and pathological data from these autopsied patients.

Results Balance disturbances occurred later in PPND than in CPSP (2.7±1.6 vs. 1.5±1.3 years; p=0.0200). Unprovoked falls presented later in PPND than in EPSP and CPSP (4.1±1. vs. 2.7±1.2 vs. 1.5±0.7 years; p<0.001), and PPND patients were wheelchair- bound later (6.0±1.9 vs. 4.9±1.3 vs. 4.1±1.0 years; p=0.008). PPND patients were more likely to exhibit pyramidal signs (47.1 vs. 5.6 vs. 0%; p=<0.001), olfactory disturbances (41.2 vs. 11.1 vs. 5.3%, p=0.013) and benefits from dopaminergic treatment were more frequent (56.9 vs. 16.7 vs. 5.3%; p=0.0015). Neuropathological findings revealed lower brain weight in PPND compared to EPSP (1100±90 vs. 1240±160g; p=0.0024), with a lower Braak neurofibrillary tangle stage in PPND (0 [0,I]) compared to EPSP (II [I,III]; p=0.007) and CPSP (III [II,III]; p<0.001). Tau severity in neuronal and glial cells was comparable between EPSP and CPSP; however, it was more severe in PPND compared to both EPSP and CPSP in the temporal cortex, frontal cortex, and basal ganglia.

Conclusions Clinically, PPND differs significantly from sporadic PSP, early symptoms may be indicative of Parkinson's disease, with PSP-like symptoms developing as the disease progresses. Pathologically, while both diseases share tau pathology, PPND exhibits more severe tau pathology in the cortices and basal ganglia.

Authors/Disclosures
Zbigniew K. Wszolek, MD, FAAN (Mayo Clinic- Jacksonville) PRESENTER	Dr. Wszolek has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Polish Neurological Society/Via Medica. Dr. Wszolek has received intellectual property interests from a discovery or technology relating to health care.
Tomasz Chmiela, MD	Dr. Chmiela has nothing to disclose.
Hiroaki Sekiya, MD, PhD (Mayo Clinic)	Dr. Sekiya has nothing to disclose.
Philip W. Tipton, MD	Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Alzheimer's Tennessee. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Charlotte County Medical Society, Inc.
Dennis W. Dickson, MD (Mayo Clinic)	Dr. Dickson has nothing to disclose.

��ɫ��

��ɫ��