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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Acta+Neuropathol+Commun
2013 ; 1
(1
): 77
Nephropedia Template TP
gab.com Text
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English Wikipedia
The type of A?-related neuronal degeneration differs between amyloid precursor
protein (APP23) and amyloid ?-peptide (APP48) transgenic mice
#MMPMID24252227
Rijal Upadhaya A
; Scheibe F
; Kosterin I
; Abramowski D
; Gerth J
; Kumar S
; Liebau S
; Yamaguchi H
; Walter J
; Staufenbiel M
; Thal DR
Acta Neuropathol Commun
2013[Nov]; 1
(1
): 77
PMID24252227
show ga
BACKGROUND: The deposition of the amyloid ?-peptide (A?) in the brain is one of
the hallmarks of Alzheimer's disease (AD). It is not yet clear whether A? always
leads to similar changes or whether it induces different features of
neurodegeneration in relation to its intra- and/or extracellular localization or
to its intracellular trafficking routes. To address this question, we have
analyzed two transgenic mouse models: APP48 and APP23 mice. The APP48 mouse
expresses A?1-42 with a signal sequence in neurons. These animals produce
intracellular A? independent of amyloid precursor protein (APP) but do not
develop extracellular A? plaques. The APP23 mouse overexpresses human APP with
the Swedish mutation (KM670/671NL) in neurons and produces APP-derived
extracellular A? plaques and intracellular A? aggregates. RESULTS: Tracing of
commissural neurons in layer III of the frontocentral cortex with the DiI tracer
revealed no morphological signs of dendritic degeneration in APP48 mice compared
to littermate controls. In contrast, the dendritic tree of highly ramified
commissural frontocentral neurons was altered in 15-month-old APP23 mice. The
density of asymmetric synapses in the frontocentral cortex was reduced in 3- and
15-month-old APP23 but not in 3- and 18-month-old APP48 mice. Frontocentral
neurons of 18-month-old APP48 mice showed an increased proportion of altered
mitochondria in the soma compared to wild type and APP23 mice. A? was often seen
in the membrane of neuronal mitochondria in APP48 mice at the ultrastructural
level. CONCLUSIONS: These results indicate that APP-independent intracellular A?
accumulation in APP48 mice is not associated with dendritic and neuritic
degeneration but with mitochondrial alterations whereas APP-derived extra- and
intracellular A? pathology in APP23 mice is linked to dendrite degeneration and
synapse loss independent of obvious mitochondrial alterations. Thus, A?
aggregates in APP23 and APP48 mice induce neurodegeneration presumably by
different mechanisms and APP-related production of A? may, thereby, play a role
for the degeneration of neurites and synapses.