A Specific Reduction in A beta(1-42) vs. a Universal Loss of A beta Peptides in CSF Differentiates Alzheimer's Disease From Meningitis and Multiple Sclerosis

Spitzer, Philipp; Lang, Roland; Oberstein, Timo J.; Lewczuk, Piotr; Ermann, Natalia; Huttner, Hagen B.; Masouris, Ilias; Kornhuber, Johannes; Ködel, Uwe und Maler, Juan M. (2018): A Specific Reduction in A beta(1-42) vs. a Universal Loss of A beta Peptides in CSF Differentiates Alzheimer's Disease From Meningitis and Multiple Sclerosis. In: Frontiers in Aging Neuroscience, Bd. 10, 152

Abstract

A reduced concentration of A beta(1-42) in CSF is one of the established biomarkers of Alzheimer's disease Reduced CSF concentrations of A beta(1-42) have also been shown in multiple sclerosis, viral encephalitis and bacterial meningitis As neuroinflammation is one of the neuropathological hallmarks of Alzheimer's disease, an infectious origin of the disease has been proposed According to this hypothesis, amyloid pathology is a consequence of a microbial infection and the resulting immune defense Accordingly, changes in CSF levels of amyloid-beta peptides should be similar in AD and inflammatory brain diseases A beta(1-42) and A beta(1-40) levels were measured in cerebrospinal fluid by ELISA and Western blotting in 34 patients with bacterial meningitis (n = 9), multiple sclerosis (n = 5) or Alzheimer's disease (n = 9) and in suitable controls (n = 11) Reduced concentrations of A beta(1-42) were detected in patients with bacterial meningitis, multiple sclerosis and Alzheimer's disease However, due to a concurrent reduction in A beta(1-40) in multiple sclerosis and meningitis patients, the ratio of A beta(1-42)/A beta(1-40) was reduced only in the CSF of Alzheimer's disease patients Urea-SDS-PAGE followed by Western blotting revealed that all A beta peptide variants are reduced in bacterial meningitis, whereas in Alzheimer's disease, only A beta(1-42) is reduced These results have two implications First, they confirm the discriminatory diagnostic power of the A beta(1-42)/A beta(1-40) ratio Second, the differential pattern of A beta peptide reductions suggests that the amyloid pathology in meningitis and multiple sclerosis differs from that in AD and does not support the notion of AD as an infection-triggered immunopathology.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1663-4365
• Sprache: Englisch