Hippocampal sclerosis dementia with tauopathy.
In some elderly individuals with dementia, hippocampal sclerosis (HS) is the only remarkable autopsy finding. The cause of HS in this setting is puzzling, since known causes of HS such as seizures or global hypoxic-ischemic episodes are rarely present. We here describe a series of HS cases that have a widespread neuronal and/or glial tauopathy. Of 14 consecutive cases of HS, 12 had been clinically diagnosed with dementia and/or Alzheimer's disease (AD) while 2 were non-demented; 7 cases had also been clinically diagnosed with parkinsonism. In addition to HS, 6 cases also met pathologic diagnostic criteria for AD. Gallyas silver staining and immunohistochemistry with the AT8 antibody revealed a glial and/or neuronal tauopathy in 12 of 14 cases, with frequent positive neurons and/or glial cells in the neocortex, basal ganglia, thalamus and/or limbic regions; in addition, 8 of the 14 cases had argyrophilic grains. Screening for known tau mutations was negative in all cases. Western blots of sarkosyl-insoluble tau protein showed a mixture of 3- and 4-repeat forms. The results suggest that most cases of HS dementia are sporadic multisystem tauopathies; we suggest the term "hippocampal sclerosis dementia with tauopathy" (HSDT) for these.
Beach
Thomas G
TG
W. H. Civin Laboratory for Neuropathology, Sun Health Research Institute, Sun City, Ariz 85372, USA. thomas.beach@sunhealth.org
Sue
Lucia
L
Scott
Sarah
S
Layne
Kathryn
K
Newell
Amanda
A
Walker
Douglas
D
Baker
Matthew
M
Sahara
Naraju
N
Yen
Shu-Hui
SH
Hutton
Michael
M
Caselli
Richard
R
Adler
Charles
C
Connor
Donald
D
Sabbagh
Marwan
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D019581:Neuropil / Q000378:metabolism / Q000473:pathology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D012598:Sclerosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D017422:Sequence Analysis, DNA; D013194:Staining and Labeling; D024801:Tauopathies / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D001057:Apolipoproteins E; D016875:tau Proteins