A1 Refereed original research article in a scientific journal
Amyloid, tau, and astrocyte pathology in autosomal-dominant Alzheimer’s disease variants: AβPParc and PSEN1DE9
Authors: Lemoine L, Gillberg PG, Bogdanovic N, Nennesmo I, Saint-Aubertlfis L, Viitanen M, Graff C, Ingelsson M, Nordberg A
Publisher: NATURE PUBLISHING GROUP
Publication year: 2020
Journal: Molecular Psychiatry
Journal name in source: MOLECULAR PSYCHIATRY
Journal acronym: MOL PSYCHIATR
Number of pages: 11
ISSN: 1359-4184
eISSN: 1476-5578
DOI: https://doi.org/10.1038/s41380-020-0817-2
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/48798616
Autosomal-dominant Alzheimer’s disease (ADAD) may be associated with
atypical amyloid beta deposits in the brain. In vivo amyloid imaging
using 11C-Pittsburgh compound B (PiB) tracer has shown
differences in binding between brains from ADAD and sporadic Alzheimer’s
disease (sAD) patients. To gain further insight into the various
pathological characteristics of these genetic variants, we performed
large frozen hemisphere autoradiography and brain homogenate binding
assays with 3H-PiB, 3H-MK6240-3H-THK5117, and 3H-deprenyl for detection of amyloid fibrils, tau depositions, and activated astrocytes, respectively, in two AβPParc mutation carriers, one PSEN1ΔE9
mutation carrier, and three sAD cases. The results were compared with
Abeta 40, Abeta 42, AT8, and GFAP immunostaining, respectively, as well
as with Congo red and Bielschowsky. PiB showed a very low binding in AβPParc. A high binding was observed in PSEN1ΔE9 and in sAD tissues but with different binding patterns. Comparable 3H-THK5117 and 3H-deprenyl brain homogenate binding was observed for AβPParc, PSEN1ΔE9, and sAD, respectively. Some differences were observed between 3H-MK6240 and 3H-THK5117 in ADAD. A positive correlation between 3H-deprenyl and 3H-THK5117 binding was observed in AβPParc, while no such correlation was found in PSEN1ΔE9
and sAD. Our study demonstrates differences in the properties of the
amyloid plaques between two genetic variants of AD and sAD. Despite the
lack of measurable amyloid fibrils by PiB in the AβPParc cases, high regional tau and astrocyte binding was observed. The lack of correlation between 3H-deprenyl and 3H-THK5117 binding in PSEN1ΔE9 and sAD in contrast of the positive correlation observed in the AβPParc cases suggest differences in the pathological cascade between variants of AD that warrant further exploration in vivo.
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