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Neuropathological heterogeneity in frontotemporal lobar degeneration with TDP-43 proteinopathy: a quantitative study of 94 cases using principal components analysis.
- Source :
-
Journal of neural transmission (Vienna, Austria : 1996) [J Neural Transm (Vienna)] 2010 Feb; Vol. 117 (2), pp. 227-39. Date of Electronic Publication: 2009 Dec 10. - Publication Year :
- 2010
-
Abstract
- Studies suggest that frontotemporal lobar degeneration with transactive response DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP) is heterogeneous with division into four or five subtypes. To determine the degree of heterogeneity and the validity of the subtypes, we studied neuropathological variation within the frontal and temporal lobes of 94 cases of FTLD-TDP using quantitative estimates of density and principal components analysis (PCA). A PCA based on the density of TDP-43 immunoreactive neuronal cytoplasmic inclusions, oligodendroglial inclusions, neuronal intranuclear inclusions, and dystrophic neurites, surviving neurons, enlarged neurons, and vacuolation suggested that cases were not segregated into distinct subtypes. Variation in the density of the vacuoles was the greatest source of variation between cases. A PCA based on TDP-43 pathology alone suggested that cases of FTLD-TDP with progranulin (GRN) mutation segregated to some degree. The pathological phenotype of all four subtypes overlapped but subtypes 1 and 4 were the most distinctive. Cases with coexisting motor neuron disease (MND) or hippocampal sclerosis (HS) also appeared to segregate to some extent. We suggest: (1) pathological variation in FTLD-TDP is best described as a 'continuum' without clearly distinct subtypes, (2) vacuolation was the single greatest source of variation and reflects the 'stage' of the disease, and (3) within the FTLD-TDP 'continuum' cases with GRN mutation and with coexisting MND or HS may have a more distinctive pathology.
- Subjects :
- Adult
Aged
Aged, 80 and over
Brain Diseases genetics
Brain Diseases metabolism
Brain Diseases pathology
DNA-Binding Proteins metabolism
Female
Frontal Lobe metabolism
Frontotemporal Lobar Degeneration genetics
Frontotemporal Lobar Degeneration metabolism
Hippocampus
Humans
Intercellular Signaling Peptides and Proteins genetics
Male
Middle Aged
Motor Neuron Disease genetics
Motor Neuron Disease metabolism
Motor Neuron Disease pathology
Mutation
Principal Component Analysis
Progranulins
Sclerosis genetics
Sclerosis metabolism
Sclerosis pathology
TDP-43 Proteinopathies genetics
TDP-43 Proteinopathies metabolism
Temporal Lobe metabolism
Frontal Lobe pathology
Frontotemporal Lobar Degeneration pathology
TDP-43 Proteinopathies pathology
Temporal Lobe pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1435-1463
- Volume :
- 117
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of neural transmission (Vienna, Austria : 1996)
- Publication Type :
- Academic Journal
- Accession number :
- 20012109
- Full Text :
- https://doi.org/10.1007/s00702-009-0350-6