Brain amyloid-beta fragment signatures in pathological ageing and Alzheimer's disease by hybrid immunoprecipitation mass spectrometry.

Abstract

BACKGROUND:

Senile plaques in Alzheimer's disease (AD) are composed of amyloid-β (Aβ), especially N-truncated forms including Aβ4-42. These are thought to be neurotoxic. However, individuals may live for decades with biomarker evidence of cerebral β-amyloidosis (positive amyloid PET imaging and/or low cerebrospinal fluid levels of the 42 amino acid form of Aβ) without cognitive impairment. This condition may be termed pathological ageing (PA).

OBJECTIVE:

To investigate whether there is a difference in the cerebral Aβ fragment pattern in brain specimens from non-demented (PA) and demented (AD) individuals expressing the full neuropathological triad of AD (senile plaques, neurofibrillary tangles and neurodegeneration).

METHODS:

We extracted Aβ using formic acid and hybrid (6E10 and 4G8) immunoprecipitation from fresh-frozen temporal cortex tissue of 6 elderly individuals (mean age ± SD: 89 ± 3.5 years) with PA and 10 patients with AD (mean age ± SD: 72 ± 8.5 years). The full spectrum of Aβ peptides was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

RESULTS:

AD patients had generally more N-terminally truncated and pyroglutamate-modified Aβ than PA patients, whereas PA patients had on average more Aβ1-40 than AD patients.

CONCLUSION:

Senile plaques in AD may have an Aβ fragment composition distinct from PA with more N-terminally and pyroglutamate-modified Aβ peptides that may be linked to neurotoxicity.

• Authors: Erik Portelius, Tammaryn Lashley, Anni Westerlund, Rita Persson, Nick C Fox, Kaj Blennow, Tamas Revesz, Henrik Zetterberg
• Journal: Neuro-degenerative diseases (Neurodegener Dis) Vol. 15 Issue 1 Pg. 50-7 ( 2015) ISSN: 1660-2862 [Electronic] Switzerland
• PMID: 25591542 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Amyloid beta-Peptides
• Biomarkers
• Peptide Fragments

Topics

• Aged
• Aged, 80 and over
• Aging (metabolism, pathology)
• Alzheimer Disease (metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Autopsy
• Biomarkers (metabolism)
• Female
• Humans
• Immunoprecipitation
• Male
• Middle Aged
• Peptide Fragments (metabolism)
• Plaque, Amyloid (metabolism, pathology)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Temporal Lobe (metabolism, pathology)