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@ARTICLE{PagnondelaVega:904313,
author = {Pagnon de la Vega, María and Giedraitis, Vilmantas and
Michno, Wojciech and Kilander, Lena and Güner, Gökhan and
Zielinski, Mara and Löwenmark, Malin and Brundin, RoseMarie
and Danfors, Torsten and Söderberg, Linda and Alafuzoff,
Irina and Nilsson, Lars N. G. and Erlandsson, Anna and
Willbold, Dieter and Müller, Stephan A. and Schröder,
Gunnar F. and Hanrieder, Jörg and Lichtenthaler, Stefan F.
and Lannfelt, Lars and Sehlin, Dag and Ingelsson, Martin},
title = {{T}he {U}ppsala {APP} deletion causes early onset autosomal
dominant {A}lzheimer’s disease by altering {APP}
processing and increasing amyloid β fibril formation},
journal = {Science translational medicine},
volume = {13},
number = {606},
issn = {1946-6234},
address = {Washington, DC},
publisher = {AAAS},
reportid = {FZJ-2021-05883},
pages = {eabc6184},
year = {2021},
note = {ERRATUM: In the Research Article “The Uppsala APP
deletion causes early onset autosomal dominant Alzheimer’s
disease by altering APP processing and increasing amyloid-β
fibril formation”, Figure 1A shows incorrect labelling of
the three patients and Figure 1C does not display the
correct transversal FDG-PET image for patient 3. These
errors have been corrected. Line 4 of the abstract included
an incorrect statement and this has been revised to read:
“Symptoms and biomarkers are typical of sporadic AD,
except that these three patients had high cerebrospinal
fluid (CSF) Aβ42 and only modest brain pathology as
detected with amyloid-positron emission tomography”. On
page 4, left column, the text discussing Figure 4C was
imprecise and has been revised to read: “The amounts of
Aβwt1–40 and Aβwt1–42 in CSF, produced from the
nonmutated APP allele, were lower in patients with the
Uppsala APP mutation compared to healthy control subjects.
In addition, the amount of Aβwt1–40 in the CSF of
patients with the mutation was lower than in sAD cases (Fig.
4C).” The online PDF and HTML (full text) have been
updated. These corrections do not impact the interpretation
of the data or the conclusions of the paper.},
abstract = {Point mutations in the amyloid precursor protein gene (APP)
cause familial Alzheimer’s disease (AD) by increasing
generation or altering conformation of amyloid β (Aβ).
Here, we describe the Uppsala APP mutation (Δ690–695),
the first reported deletion causing autosomal dominant AD.
Affected individuals have an age at symptom onset in their
early forties and suffer from a rapidly progressing disease
course. Symptoms and biomarkers are typical of sporadic AD,
except that these three patients had high cerebrospinal
fluid (CSF) Aβ42 and only modest brain pathology as
detected by amyloid-positron emission tomography. Mass
spectrometry and Western blot analyses of patient CSF and
media from experimental cell cultures indicate that the
Uppsala APP mutation alters APP processing by increasing
β-secretase cleavage and affecting α-secretase cleavage.
Furthermore, in vitro aggregation studies and analyses of
patient brain tissue samples indicate that the longer form
of mutated Aβ, AβUpp1–42Δ19–24, accelerates the
formation of fibrils with unique polymorphs and their
deposition into amyloid plaques in the affected brain.},
cin = {IBI-7},
ddc = {500},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34380771},
UT = {WOS:000686429000003},
doi = {10.1126/scitranslmed.abc6184},
url = {https://juser.fz-juelich.de/record/904313},
}