Highly potent soluble amyloid-β seeds in human Alzheimer brain but not cerebrospinal fluid.

The soluble fraction of brain samples from patients with Alzheimer's disease contains highly biologically active amyloid-β seeds. In this study, we sought to assess the potency of soluble amyloid-β seeds derived from the brain and cerebrospinal fluid. Soluble Alzheimer's disease brain extracts were serially diluted and then injected into the hippocampus of young, APP transgenic mice. Eight months later, seeded amyloid-β deposition was evident even when the hippocampus received subattomole amounts of brain-derived amyloid-β. In contrast, cerebrospinal fluid from patients with Alzheimer's disease, which contained more than 10-fold higher levels of amyloid-β peptide than the most concentrated soluble brain extracts, did not induce detectable seeding activity in vivo. Similarly, cerebrospinal fluid from aged APP-transgenic donor mice failed to induce cerebral amyloid-β deposition. In comparison to the soluble brain fraction, cerebrospinal fluid largely lacked N-terminally truncated amyloid-β species and exhibited smaller amyloid-β-positive particles, features that may contribute to the lack of in vivo seeding by cerebrospinal fluid. Interestingly, the same cerebrospinal fluid showed at least some seeding activity in an in vitro assay. The present results indicate that the biological seeding activity of soluble amyloid-β species is orders of magnitude greater in brain extracts than in the cerebrospinal fluid.

Langer, Franziska (author)
Kaeser, Stephan A (author)
Maia, Luis F (author)
Portelius, Erik,1977Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xporer (author)
Pinotsi, Dorothea (author)
Kaminski, Clemens F (author)
Winkler, David T (author)
Maetzler, Walter (author)
Keyvani, Kathy (author)
Spitzer, Philipp (author)
Wiltfang, Jens (author)
Kaminski Schierle, Gabriele S (author)
Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe (author)
Staufenbiel, Matthias (author)
Jucker, Mathias (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

In:Brain : a journal of neurology: Oxford University Press (OUP)137:11, s. 2909-29151460-2156
In:Brain: Oxford University Press (OUP)137:11, s. 2909-29150006-8950

By the author/editor: Fritschi, Sarah ...; Langer, Franzisk ...; Kaeser, Stephan ...; Maia, Luis F; Portelius, Erik, ...; Pinotsi, Dorothe ...; show more...; Kaminski, Clemen ...; Winkler, David T; Maetzler, Walter; Keyvani, Kathy; Spitzer, Philipp; Wiltfang, Jens; Kaminski Schierl ...; Zetterberg, Henr ...; Staufenbiel, Mat ...; Jucker, Mathias; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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