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  3. Medizin - Open Access LMU - Teil 17/22 Podcast
  4. Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease
Background: Alzheimer's disease (AD) is associated with deposition
of amyloid beta (A beta) in the brain, which is reflected by low
concentration of the A beta 1-42 peptide in the cerebrospinal fluid
(CSF). There are at least 15 additional A beta peptides in human
CSF and their relative abundance pattern is thought to reflect the
production and degradation of A beta. Here, we test the hypothesis
that AD is characterized by a specific CSF A beta isoform pattern
that is distinct when comparing sporadic AD (SAD) and familial AD
(FAD) due to different mechanisms underlying brain amyloid
pathology in the two disease groups. Results: We measured A beta
isoform concentrations in CSF from 18 patients with SAD, 7 carriers
of the FAD-associated presenilin 1 (PSEN1) A431E mutation, 17
healthy controls and 6 patients with depression using
immunoprecipitation-mass spectrometry. Low CSF levels of A beta
1-42 and high levels of A beta 1-16 distinguished SAD patients and
FAD mutation carriers from healthy controls and depressed patients.
SAD and FAD were characterized by similar changes in A beta 1-42
and A beta 1-16, but FAD mutation carriers exhibited very low
levels of A beta 1-37, A beta 1-38 and A beta 1-39. Conclusion: SAD
patients and PSEN1 A431E mutation carriers are characterized by
aberrant CSF A beta isoform patterns that hold clinically relevant
diagnostic information. PSEN1 A431E mutation carriers exhibit low
levels of A beta 1-37, A beta 1-38 and A beta 1-39; fragments that
are normally produced by gamma-secretase, suggesting that the PSEN1
A431E mutation modulates gamma-secretase cleavage site preference
in a disease-promoting manner.

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„Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease“

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