Neuropathologic Heterogeneity in HDDD1: A Familial Frontotemporal Lobar Degeneration With Ubiquitin-positive Inclusions and Progranulin Mutation
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2007-03Metadata
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Behrens Pellegrino, María Isabel
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Neuropathologic Heterogeneity in HDDD1: A Familial Frontotemporal Lobar Degeneration With Ubiquitin-positive Inclusions and Progranulin Mutation
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Abstract
Hereditary dysphasic disinhibition dementia (HDDD)
describes a familial disorder characterized by personality
changes, and language and memory deficits. The neuropathology
includes frontotemporal lobar atrophy, neuronal loss and
gliosis and, in most cases, abundant Ab plaques and neurofibrillary
tangles (NFTs). A Pick/Alzheimer’s spectrum was
proposed for the original family (HDDD1). Here we report
the clinicopathologic case of an HDDD1 individual using
modern immunohistochemical methods, contemporary neuropathologic
diagnostic criteria to distinguish different frontotemporal
lobar degenerations (FTLDs), and progranulin (PRGN)
mutation analysis. Clinical onset was at age 62 years with
personality changes and disinhibition, followed by nonfluent
dysphasia, and memory loss that progressed to muteness and
total dependence with death at age 84 years. There was severe
generalized brain atrophy (weight=570 g). Histopathology
showed superficial microvacuolation, marked neuronal loss,
gliosis, and ubiquitin-positive, tau-negative cytoplasmic and
intranuclear neuronal inclusions in frontal, temporal, and
parietal cortices. There were also frequent neuritic plaques and
NFTs in parietal and occipital cortices. The case met
neuropathologic criteria for both FTLD with ubiquitin-positive,
tau-negative inclusions (FTLD-U), and Alzheimer disease (Braak NFT stage V). We discovered a novel pathogenic PGRN
mutation c.5913 A>G (IVS6-2 A>G) segregating with FTLDU
in this kindred. In conclusion, HDDD1 is an FTLD-U caused
by a PGRN mutation and is neuropathologically heterogeneous
with Alzheimer disease as a common comorbidity.
Patrocinador
Support by grants from the National Institute on Aging of the National
Institutes of Health (P01 AG-03991 and P50 AG-05681). Odity
Mukherjee is a Fogarty International Postdoctoral fellow (Grant No.
TW 0511-05). Rajka M. Liscic was supported by a J. William
Fulbright Foreign Scholarship (Grant No. 68428174).
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URI: https://repositorio.uchile.cl/handle/2250/128491
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Alzheimer Dis Assoc Disord - Volume 21, Number 1, January–March 2007
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