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Distinct deposition of amyloid-β species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry

Overview of attention for article published in Acta Neuropathologica Communications, October 2017
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Title
Distinct deposition of amyloid-β species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry
Published in
Acta Neuropathologica Communications, October 2017
DOI 10.1186/s40478-017-0477-x
Pubmed ID
Authors

Nobuto Kakuda, Tomohiro Miyasaka, Noriyuki Iwasaki, Takashi Nirasawa, Satoko Wada-Kakuda, Junko Takahashi-Fujigasaki, Shigeo Murayama, Yasuo Ihara, Masaya Ikegawa

Abstract

Amyloid β (Aβ) deposition in the brain is an early and invariable feature of Alzheimer's disease (AD). The Aβ peptides are composed of about 40 amino acids and are generated from amyloid precursor proteins (APP), by β- and γ-secretases. The distribution of individual Aβ peptides in the brains of aged people, and those suffering from AD and cerebral amyloid angiopathy (CAA), is not fully characterized. We employed the matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) to illustrate the spatial distribution of a broad range of Aβ species in human autopsied brains. With technical advancements such as formic acid pretreatment of frozen autopsied brain samples, we have: i) demonstrated that Aβ1-42 and Aβ1-43 were selectively deposited in senile plaques while full-length Aβ peptides such as Aβ1-36, 1-37, 1-38, 1-39, 1-40, and Aβ1-41 were deposited in leptomeningeal blood vessels. ii) Visualized distinct depositions of N-terminal truncated Aβ40 and Aβ42, including pyroglutamate modified at Glu-3 (N3pE), only with IMS for the first time. iii) Demonstrated that one single amino acid alteration at the C-terminus between Aβ1-42 and Aβ1-41 results in profound changes in their distribution pattern. In vitro, this can be attributed to the difference in the self-aggregation ability amongst Aβ1-40, Aβ1-41, and Aβ1-42. These observations were further confirmed with immunohistochemistry (IHC), using the newly developed anti-Aβ1-41 antibody. Here, distinct depositions of truncated and/or modified C- and N-terminal fragments of Aβs in AD and CAA brains with MALDI-IMS were visualized in a spacio-temporal specific manner. Specifically, Aβ1-41 was detected both with MALDI-IMS and IHC suggesting that a single amino acid alteration at the C-terminus of Aβ results in drastic distribution changes. These results suggest that MALDI-IMS could be used as a standard approach in combination with clinical, genetic, and pathological observations in understanding the pathology of AD and CAA.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 59 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 59 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 14 24%
Student > Ph. D. Student 10 17%
Student > Master 6 10%
Student > Bachelor 6 10%
Other 5 8%
Other 7 12%
Unknown 11 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 24%
Medicine and Dentistry 7 12%
Agricultural and Biological Sciences 7 12%
Neuroscience 7 12%
Chemistry 5 8%
Other 6 10%
Unknown 13 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 December 2017.
All research outputs
#7,353,636
of 12,247,570 outputs
Outputs from Acta Neuropathologica Communications
#356
of 537 outputs
Outputs of similar age
#148,711
of 286,759 outputs
Outputs of similar age from Acta Neuropathologica Communications
#32
of 45 outputs
Altmetric has tracked 12,247,570 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 537 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one is in the 30th percentile – i.e., 30% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 286,759 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 45 others from the same source and published within six weeks on either side of this one. This one is in the 24th percentile – i.e., 24% of its contemporaries scored the same or lower than it.