Independent accumulations of tau and amyloid beta-protein in the human entorhinal cortex.
BACKGROUND
Previous studies have repeatedly described that neurofibrillary tangles arise earlier than senile plaques (SPs) in the entorhinal cortex, but one study suggested that SPs, if present, enhance the former lesions. All of these studies were performed at the histologic or immunocytochemical level, which may not accurately reflect the actual levels of amyloid beta-protein (Abeta) and tau.


OBJECTIVE
To determine whether there is significant interaction between Abeta and tau in the human entorhinal cortex with regard to the Braak stage.


METHODS
Biochemical studies were conducted on 50 brains from elderly people, who were mainly at Braak stages I to III. All the cases were examined neuropathologically and staged according to Braak and Braak. A small piece of brain tissue for each case was dissected from the anterior portion of the right entorhinal cortex. The amounts of tau and Abeta in the insoluble fraction of the tissue were quantified using western blotting.


RESULTS
The levels of tau and possibly Abeta42 in the entorhinal cortex appeared to rise steeply at approximately age 75. The levels of insoluble tau increased as the Braak stage increased from I to II; however, it had a tendency to remain between stages II and III. The levels of Abeta42 showed a small increase, whereas those of Abeta40 increased continuously as the Braak stage advanced. In contrast, the extent of Abeta42 accumulation increased with increasing Braak stage for SPs. There was no significant correlation between the levels of insoluble tau and Abeta42 in the entorhinal cortex. Even if Abeta did not accumulate to significant extents, substantial accumulation of insoluble tau occurred.


CONCLUSIONS
Accumulations of tau and amyloid beta-protein occur independently in the human entorhinal cortex.
Katsuno
T
T
Department of Neuropathology, Faculty of Medicine, Graduate School of Arts and Science, University of Tokyo, Tokyo, Japan.
Morishima-Kawashima
M
M
Saito
Y
Y
Yamanouchi
H
H
Ishiura
S
S
Murayama
S
S
Ihara
Y
Y
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000032:analysis*; D015153:Blotting, Western; D018450:Disease Progression; D018728:Entorhinal Cortex / Q000737:chemistry*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000737:chemistry; D010446:Peptide Fragments / Q000032:analysis*; D058225:Plaque, Amyloid / Q000737:chemistry; D012995:Solubility; D016875:tau Proteins / Q000032:analysis*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins