'Tri-ortho-cresyl phosphate (ToCP) is a multipurpose organophosphorus compound that is neurotoxic and suspected to be involved in aerotoxic syndrome in humans. It has been reported that not ToCP itself but a metabolite of ToCP, namely, 2-(ortho-cresyl)-4H-1,2,3-benzodioxaphosphoran-2-one (CBDP), may be responsible for this effect as it can irreversibly bind to human ... More
Characterization of the postsynaptic protein neurogranin in paired cerebrospinal fluid and plasma samples from Alzheimer's disease patients and healthy controls.
AuthorsKvartsberg H, Portelius E, Andreasson U, Brinkmalm G, Hellwig K, Lelental N, Kornhuber J, Hansson O, Minthon L, Spitzer P, Maler JM, Zetterberg H, Blennow K, Lewczuk P
Journal
PubMed ID26136856
'Synaptic dysfunction and degeneration are central events in Alzheimer''s disease (AD) pathophysiology that are thought to occur early in disease progression. Synaptic pathology may be studied by examining protein biomarkers specific for different synaptic elements. We recently showed that the dendritic protein neurogranin (Ng), including the endogenous Ng peptide 48 ... More
Brain amyloid-beta fragment signatures in pathological ageing and Alzheimer's disease by hybrid immunoprecipitation mass spectrometry.
AuthorsPortelius E, Lashley T, Westerlund A, Persson R, Fox NC, Blennow K, Revesz T, Zetterberg H
Journal
PubMed ID25591542
'Senile plaques in Alzheimer''s disease (AD) are composed of amyloid-ß (Aß), especially N-truncated forms including Aß4-42. These are thought to be neurotoxic. However, individuals may live for decades with biomarker evidence of cerebral ß-amyloidosis (positive amyloid PET imaging and/or low cerebrospinal fluid levels of the 42 amino acid form of ... More
APP metabolism regulates tau proteostasis in human cerebral cortex neurons.
AuthorsMoore S, Evans LD, Andersson T, Portelius E, Smith J, Dias TB, Saurat N, McGlade A, Kirwan P, Blennow K, Hardy J, Zetterberg H, Livesey FJ
Journal
PubMed ID25921538
'Accumulation of Aß peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer''s disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of ... More
Highly potent soluble amyloid-ß seeds in human Alzheimer brain but not cerebrospinal fluid.
AuthorsFritschi SK, Langer F, Kaeser SA, Maia LF, Portelius E, Pinotsi D, Kaminski CF, Winkler DT, Maetzler W, Keyvani K, Spitzer P, Wiltfang J, Kaminski Schierle GS, Zetterberg H, Staufenbiel M, Jucker M
Journal
PubMed ID25212850
The soluble fraction of brain samples from patients with Alzheimer's disease contains highly biologically active amyloid-ß seeds. In this study, we sought to assess the potency of soluble amyloid-ß seeds derived from the brain and cerebrospinal fluid. Soluble Alzheimer's disease brain extracts were serially diluted and then injected into the ... More
Targeting LAMP2 in human cerebrospinal fluid with a combination of immunopurification and high resolution parallel reaction monitoring mass spectrometry.
AuthorsSjödin S, Öhrfelt A, Brinkmalm G, Zetterberg H, Blennow K, Brinkmalm A
JournalClin Proteomics
PubMed ID26924951
Alzheimer's disease is the most common form of dementia. An increasing body of evidence suggests that endo-lysosomal dysfunction is a pathogenic mechanism of Alzheimer's disease. Thus there is a potential for proteins involved in the normal function of endo-lysosomal vesicles to act as biomarkers of disease. Herein we focused on ... More