Abstract
Reinvestigation of the chemical structure of β-amyloid peptide (Aβ) deposits in the vascular tissue of Alzheimer disease brains revealed that the 42-residue form Aβ-(1-42), rather than the more soluble Aβ-(1-40) form, is the predominant peptide. Following removal of the surrounding tissue with SDS and collagenase, Aβ was solubilized in formic acid and purified by Superose 12 chromatography. Peptides generated by enzymatic and chemical digestion of the Aβ were purified by HPLC and characterized by amino acid analysis, sequence analysis, and mass spectrometry. In the leptomeningeal vessels, the average ratio of Aβ-(1-42)/Aβ-(1-40) was 58:42, whereas in the parenchymal vessels this ratio was 75:25. Interestingly, vascular Aβ contains considerably less isomerized and racemized aspartyl residues than does neuritic plaque Aβ, suggesting that the vascular amyloid is "younger." The discrete nature of the bands and spherical deposits of Aβ associated with arterioles and capillaries, respectively, suggests that this amyloid arises from the vascular tissue itself. Increasing Aβ deposition appears to lead to the distortion and occlusion of capillaries, which may contribute significantly to the pathology of Alzheimer disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 10836-10840 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 90 |
| Issue number | 22 |
| State | Published - Nov 15 1993 |
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Keywords
- Blood brain barrier
- Cerebrovasculature
ASJC Scopus subject areas
- General
- Genetics
Cite this
β-amyloid-(1-42) is a major component of cerebrovascular amyloid deposits : Implications for the pathology of Alzheimer disease. / Roher, Alex E.; Lowenson, Jonathan D.; Clarke, Steven; Woods, Amina S.; Cotter, Robert J.; Gowing, Eric; Ball, Melvyn J.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 22, 15.11.1993, p. 10836-10840.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - β-amyloid-(1-42) is a major component of cerebrovascular amyloid deposits
T2 - Implications for the pathology of Alzheimer disease
AU - Roher, Alex E.
AU - Lowenson, Jonathan D.
AU - Clarke, Steven
AU - Woods, Amina S.
AU - Cotter, Robert J.
AU - Gowing, Eric
AU - Ball, Melvyn J.
PY - 1993/11/15
Y1 - 1993/11/15
N2 - Reinvestigation of the chemical structure of β-amyloid peptide (Aβ) deposits in the vascular tissue of Alzheimer disease brains revealed that the 42-residue form Aβ-(1-42), rather than the more soluble Aβ-(1-40) form, is the predominant peptide. Following removal of the surrounding tissue with SDS and collagenase, Aβ was solubilized in formic acid and purified by Superose 12 chromatography. Peptides generated by enzymatic and chemical digestion of the Aβ were purified by HPLC and characterized by amino acid analysis, sequence analysis, and mass spectrometry. In the leptomeningeal vessels, the average ratio of Aβ-(1-42)/Aβ-(1-40) was 58:42, whereas in the parenchymal vessels this ratio was 75:25. Interestingly, vascular Aβ contains considerably less isomerized and racemized aspartyl residues than does neuritic plaque Aβ, suggesting that the vascular amyloid is "younger." The discrete nature of the bands and spherical deposits of Aβ associated with arterioles and capillaries, respectively, suggests that this amyloid arises from the vascular tissue itself. Increasing Aβ deposition appears to lead to the distortion and occlusion of capillaries, which may contribute significantly to the pathology of Alzheimer disease.
AB - Reinvestigation of the chemical structure of β-amyloid peptide (Aβ) deposits in the vascular tissue of Alzheimer disease brains revealed that the 42-residue form Aβ-(1-42), rather than the more soluble Aβ-(1-40) form, is the predominant peptide. Following removal of the surrounding tissue with SDS and collagenase, Aβ was solubilized in formic acid and purified by Superose 12 chromatography. Peptides generated by enzymatic and chemical digestion of the Aβ were purified by HPLC and characterized by amino acid analysis, sequence analysis, and mass spectrometry. In the leptomeningeal vessels, the average ratio of Aβ-(1-42)/Aβ-(1-40) was 58:42, whereas in the parenchymal vessels this ratio was 75:25. Interestingly, vascular Aβ contains considerably less isomerized and racemized aspartyl residues than does neuritic plaque Aβ, suggesting that the vascular amyloid is "younger." The discrete nature of the bands and spherical deposits of Aβ associated with arterioles and capillaries, respectively, suggests that this amyloid arises from the vascular tissue itself. Increasing Aβ deposition appears to lead to the distortion and occlusion of capillaries, which may contribute significantly to the pathology of Alzheimer disease.
KW - Blood brain barrier
KW - Cerebrovasculature
UR - http://www.scopus.com/inward/record.url?scp=0027332081&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027332081&partnerID=8YFLogxK
M3 - Article
C2 - 8248178
AN - SCOPUS:0027332081
VL - 90
SP - 10836
EP - 10840
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 22
ER -