Increased γ-secretase activity in idiopathic normal pressure hydrocephalus patients with β-amyloid pathology.
The potential similarity between the brain pathology of idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer disease (AD) is intriguing and thus further studies focusing on the underlying molecular mechanisms may offer valuable information for differential diagnostics and the development of treatments for iNPH. Here, we investigated β- and γ-secretase activities in relation to amyloid-β (Aβ) pathology in the brain tissue samples collected from iNPH and AD patients. β- and γ-secretase activities were measured from the frontal cortical biopsies of 26 patients with suspected iNPH as well as post-mortem tissue samples from the inferior temporal cortex of 74 AD patients and eight subjects without neurofibrillary pathology. In iNPH samples with detectable Aβ plaques, γ-secretase activity was significantly increased (∼ 1.6-fold) when compared to iNPH samples without Aβ plaques (p = 0.009). In the AD samples, statistically significant differences in the γ-secretase activity were not observed with respect to disease severity (mild, moderate and severe AD according to neurofibrillary pathology). Conversely, β-secretase activity was unaltered in iNPH samples with or without Aβ plaques, while it was significantly increased in relation to disease severity in the AD patients. These results show for the first time increased γ-secretase but not β-secretase activity in the biopsy samples from the frontal cortex of iNPH patients with AD-like Aβ pathology. Conversely, the opposite was observed in these secretase activities in AD patients with respect to neurofibrillary pathology. Despite the resemblances in the Aβ pathology, iNPH and AD patients appear to have marked differences in the cellular mechanisms responsible for the production of Aβ.
Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, Kuopio, Finland; Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
Tiina
T
Laiterä
Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
Timo
T
Sarajärvi
Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
Annakaisa
A
Haapasalo
A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
Lakshman
L
Puli
Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
Tarja
T
Kauppinen
Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
Petra
P
Mäkinen
Institute of Clinical Medicine - Pathology, University of Eastern Finland, Kuopio, Finland; Department of Pathology, Kuopio University Hospital, Kuopio, Finland.
Tuomas
T
Rauramaa
A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
Heikki
H
Tanila
Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, Kuopio, Finland; Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
Juha E
JE
Jääskeläinen
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Irina
I
Alafuzoff
Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland; Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
Hilkka
H
Soininen
Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, Kuopio, Finland; Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
Ville
V
Leinonen
Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
Mikko
M
Hiltunen
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000378:metabolism* / Q000473:pathology; D008297:Male
D016229:Amyloid beta-Peptides; D053829:Amyloid Precursor Protein Secretases