BIOMAT Database Logo BIOMAT Database Logo

Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer's disease. 2022

Pieter Jelle Visser, and Lianne M Reus, and Johan Gobom, and Iris Jansen, and Ellen Dicks, and Sven J van der Lee, and Magda Tsolaki, and Frans R J Verhey, and Julius Popp, and Pablo Martinez-Lage, and Rik Vandenberghe, and Alberto Lleó, and José Luís Molinuevo, and Sebastiaan Engelborghs, and Yvonne Freund-Levi, and Lutz Froelich, and Kristel Sleegers, and Valerija Dobricic, and Simon Lovestone, and Johannes Streffer, and Stephanie J B Vos, and Isabelle Bos, and , and August B Smit, and Kaj Blennow, and Philip Scheltens, and Charlotte E Teunissen, and Lars Bertram, and Henrik Zetterberg, and Betty M Tijms
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, PO Box 7057 1007, MB, Amsterdam, The Netherlands. pj.visser@amsterdamumc.nl.

Increased total tau (t-tau) in cerebrospinal fluid (CSF) is a key characteristic of Alzheimer's disease (AD) and is considered to result from neurodegeneration. T-tau levels, however, can be increased in very early disease stages, when neurodegeneration is limited, and can be normal in advanced disease stages. This suggests that t-tau levels may be driven by other mechanisms as well. Because tau pathophysiology is emerging as treatment target for AD, we aimed to clarify molecular processes associated with CSF t-tau levels. We performed a proteomic, genomic, and imaging study in 1380 individuals with AD, in the preclinical, prodromal, and mild dementia stage, and 380 controls from the Alzheimer's Disease Neuroimaging Initiative and EMIF-AD Multimodality Biomarker Discovery study. We found that, relative to controls, AD individuals with increased t-tau had increased CSF concentrations of over 400 proteins enriched for neuronal plasticity processes. In contrast, AD individuals with normal t-tau had decreased levels of these plasticity proteins and showed increased concentrations of proteins indicative of blood-brain barrier and blood-CSF barrier dysfunction, relative to controls. The distinct proteomic profiles were already present in the preclinical AD stage and persisted in prodromal and dementia stages implying that they reflect disease traits rather than disease states. Dysregulated plasticity proteins were associated with SUZ12 and REST signaling, suggesting aberrant gene repression. GWAS analyses contrasting AD individuals with and without increased t-tau highlighted several genes involved in the regulation of gene expression. Targeted analyses of SNP rs9877502 in GMNC, associated with t-tau levels previously, correlated in individuals with AD with CSF concentrations of 591 plasticity associated proteins. The number of APOE-e4 alleles, however, was not associated with the concentration of plasticity related proteins. CSF t-tau levels in AD are associated with altered levels of proteins involved in neuronal plasticity and blood-brain and blood-CSF barrier dysfunction. Future trials may need to stratify on CSF t-tau status, as AD individuals with increased t-tau and normal t-tau are likely to respond differently to treatment, given their opposite CSF proteomic profiles.

UI MeSH Term Description Entries
D009473 Neuronal Plasticity The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations. Brain Plasticity,Plasticity, Neuronal,Axon Pruning,Axonal Pruning,Dendrite Arborization,Dendrite Pruning,Dendritic Arborization,Dendritic Pruning,Dendritic Remodeling,Neural Plasticity,Neurite Pruning,Neuronal Arborization,Neuronal Network Remodeling,Neuronal Pruning,Neuronal Remodeling,Neuroplasticity,Synaptic Plasticity,Synaptic Pruning,Arborization, Dendrite,Arborization, Dendritic,Arborization, Neuronal,Arborizations, Dendrite,Arborizations, Dendritic,Arborizations, Neuronal,Axon Prunings,Axonal Prunings,Brain Plasticities,Dendrite Arborizations,Dendrite Prunings,Dendritic Arborizations,Dendritic Prunings,Dendritic Remodelings,Network Remodeling, Neuronal,Network Remodelings, Neuronal,Neural Plasticities,Neurite Prunings,Neuronal Arborizations,Neuronal Network Remodelings,Neuronal Plasticities,Neuronal Prunings,Neuronal Remodelings,Neuroplasticities,Plasticities, Brain,Plasticities, Neural,Plasticities, Neuronal,Plasticities, Synaptic,Plasticity, Brain,Plasticity, Neural,Plasticity, Synaptic,Pruning, Axon,Pruning, Axonal,Pruning, Dendrite,Pruning, Dendritic,Pruning, Neurite,Pruning, Neuronal,Pruning, Synaptic,Prunings, Axon,Prunings, Axonal,Prunings, Dendrite,Prunings, Dendritic,Prunings, Neurite,Prunings, Neuronal,Prunings, Synaptic,Remodeling, Dendritic,Remodeling, Neuronal,Remodeling, Neuronal Network,Remodelings, Dendritic,Remodelings, Neuronal,Remodelings, Neuronal Network,Synaptic Plasticities,Synaptic Prunings
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000544 Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D016875 tau Proteins Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES). tau Protein,Protein, tau,Proteins, tau
D040901 Proteomics The systematic study of the complete complement of proteins (PROTEOME) of organisms. Peptidomics

Related Publications

Pieter Jelle Visser, and Lianne M Reus, and Johan Gobom, and Iris Jansen, and Ellen Dicks, and Sven J van der Lee, and Magda Tsolaki, and Frans R J Verhey, and Julius Popp, and Pablo Martinez-Lage, and Rik Vandenberghe, and Alberto Lleó, and José Luís Molinuevo, and Sebastiaan Engelborghs, and Yvonne Freund-Levi, and Lutz Froelich, and Kristel Sleegers, and Valerija Dobricic, and Simon Lovestone, and Johannes Streffer, and Stephanie J B Vos, and Isabelle Bos, and , and August B Smit, and Kaj Blennow, and Philip Scheltens, and Charlotte E Teunissen, and Lars Bertram, and Henrik Zetterberg, and Betty M Tijms
Vascular risk factors are associated with longitudinal changes in cerebrospinal fluid tau markers and cognition in preclinical Alzheimer's disease.
September 2019, Alzheimer's & dementia : the journal of the Alzheimer's Association,
Pieter Jelle Visser, and Lianne M Reus, and Johan Gobom, and Iris Jansen, and Ellen Dicks, and Sven J van der Lee, and Magda Tsolaki, and Frans R J Verhey, and Julius Popp, and Pablo Martinez-Lage, and Rik Vandenberghe, and Alberto Lleó, and José Luís Molinuevo, and Sebastiaan Engelborghs, and Yvonne Freund-Levi, and Lutz Froelich, and Kristel Sleegers, and Valerija Dobricic, and Simon Lovestone, and Johannes Streffer, and Stephanie J B Vos, and Isabelle Bos, and , and August B Smit, and Kaj Blennow, and Philip Scheltens, and Charlotte E Teunissen, and Lars Bertram, and Henrik Zetterberg, and Betty M Tijms
Tau phosphorylation pathway genes and cerebrospinal fluid tau levels in Alzheimer's disease.
October 2012, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics,
Pieter Jelle Visser, and Lianne M Reus, and Johan Gobom, and Iris Jansen, and Ellen Dicks, and Sven J van der Lee, and Magda Tsolaki, and Frans R J Verhey, and Julius Popp, and Pablo Martinez-Lage, and Rik Vandenberghe, and Alberto Lleó, and José Luís Molinuevo, and Sebastiaan Engelborghs, and Yvonne Freund-Levi, and Lutz Froelich, and Kristel Sleegers, and Valerija Dobricic, and Simon Lovestone, and Johannes Streffer, and Stephanie J B Vos, and Isabelle Bos, and , and August B Smit, and Kaj Blennow, and Philip Scheltens, and Charlotte E Teunissen, and Lars Bertram, and Henrik Zetterberg, and Betty M Tijms
Cerebrospinal fluid levels of A beta 42 and tau: potential markers of Alzheimer's disease.
January 1998, Journal of neural transmission. Supplementum,
Pieter Jelle Visser, and Lianne M Reus, and Johan Gobom, and Iris Jansen, and Ellen Dicks, and Sven J van der Lee, and Magda Tsolaki, and Frans R J Verhey, and Julius Popp, and Pablo Martinez-Lage, and Rik Vandenberghe, and Alberto Lleó, and José Luís Molinuevo, and Sebastiaan Engelborghs, and Yvonne Freund-Levi, and Lutz Froelich, and Kristel Sleegers, and Valerija Dobricic, and Simon Lovestone, and Johannes Streffer, and Stephanie J B Vos, and Isabelle Bos, and , and August B Smit, and Kaj Blennow, and Philip Scheltens, and Charlotte E Teunissen, and Lars Bertram, and Henrik Zetterberg, and Betty M Tijms
SNPs associated with cerebrospinal fluid phospho-tau levels influence rate of decline in Alzheimer's disease.
September 2010, PLoS genetics,
Pieter Jelle Visser, and Lianne M Reus, and Johan Gobom, and Iris Jansen, and Ellen Dicks, and Sven J van der Lee, and Magda Tsolaki, and Frans R J Verhey, and Julius Popp, and Pablo Martinez-Lage, and Rik Vandenberghe, and Alberto Lleó, and José Luís Molinuevo, and Sebastiaan Engelborghs, and Yvonne Freund-Levi, and Lutz Froelich, and Kristel Sleegers, and Valerija Dobricic, and Simon Lovestone, and Johannes Streffer, and Stephanie J B Vos, and Isabelle Bos, and , and August B Smit, and Kaj Blennow, and Philip Scheltens, and Charlotte E Teunissen, and Lars Bertram, and Henrik Zetterberg, and Betty M Tijms
Increased cerebrospinal fluid tau levels in logopenic variant of Alzheimer's disease.
January 2014, Journal of Alzheimer's disease : JAD,
Pieter Jelle Visser, and Lianne M Reus, and Johan Gobom, and Iris Jansen, and Ellen Dicks, and Sven J van der Lee, and Magda Tsolaki, and Frans R J Verhey, and Julius Popp, and Pablo Martinez-Lage, and Rik Vandenberghe, and Alberto Lleó, and José Luís Molinuevo, and Sebastiaan Engelborghs, and Yvonne Freund-Levi, and Lutz Froelich, and Kristel Sleegers, and Valerija Dobricic, and Simon Lovestone, and Johannes Streffer, and Stephanie J B Vos, and Isabelle Bos, and , and August B Smit, and Kaj Blennow, and Philip Scheltens, and Charlotte E Teunissen, and Lars Bertram, and Henrik Zetterberg, and Betty M Tijms
Alzheimer's disease with abnormal cerebrospinal fluid flow.
October 1973, Neurology,
Pieter Jelle Visser, and Lianne M Reus, and Johan Gobom, and Iris Jansen, and Ellen Dicks, and Sven J van der Lee, and Magda Tsolaki, and Frans R J Verhey, and Julius Popp, and Pablo Martinez-Lage, and Rik Vandenberghe, and Alberto Lleó, and José Luís Molinuevo, and Sebastiaan Engelborghs, and Yvonne Freund-Levi, and Lutz Froelich, and Kristel Sleegers, and Valerija Dobricic, and Simon Lovestone, and Johannes Streffer, and Stephanie J B Vos, and Isabelle Bos, and , and August B Smit, and Kaj Blennow, and Philip Scheltens, and Charlotte E Teunissen, and Lars Bertram, and Henrik Zetterberg, and Betty M Tijms
Increased cerebrospinal fluid tau in patients with Alzheimer's disease.
February 1995, Neuroscience letters,
Pieter Jelle Visser, and Lianne M Reus, and Johan Gobom, and Iris Jansen, and Ellen Dicks, and Sven J van der Lee, and Magda Tsolaki, and Frans R J Verhey, and Julius Popp, and Pablo Martinez-Lage, and Rik Vandenberghe, and Alberto Lleó, and José Luís Molinuevo, and Sebastiaan Engelborghs, and Yvonne Freund-Levi, and Lutz Froelich, and Kristel Sleegers, and Valerija Dobricic, and Simon Lovestone, and Johannes Streffer, and Stephanie J B Vos, and Isabelle Bos, and , and August B Smit, and Kaj Blennow, and Philip Scheltens, and Charlotte E Teunissen, and Lars Bertram, and Henrik Zetterberg, and Betty M Tijms
Tau oligomers in cerebrospinal fluid in Alzheimer's disease.
April 2017, Annals of clinical and translational neurology,
Pieter Jelle Visser, and Lianne M Reus, and Johan Gobom, and Iris Jansen, and Ellen Dicks, and Sven J van der Lee, and Magda Tsolaki, and Frans R J Verhey, and Julius Popp, and Pablo Martinez-Lage, and Rik Vandenberghe, and Alberto Lleó, and José Luís Molinuevo, and Sebastiaan Engelborghs, and Yvonne Freund-Levi, and Lutz Froelich, and Kristel Sleegers, and Valerija Dobricic, and Simon Lovestone, and Johannes Streffer, and Stephanie J B Vos, and Isabelle Bos, and , and August B Smit, and Kaj Blennow, and Philip Scheltens, and Charlotte E Teunissen, and Lars Bertram, and Henrik Zetterberg, and Betty M Tijms
[Cerebrospinal fluid protein tau levels in the differential diagnosis of Alzheimer's disease].
October 2000, Fortschritte der Neurologie-Psychiatrie,
Pieter Jelle Visser, and Lianne M Reus, and Johan Gobom, and Iris Jansen, and Ellen Dicks, and Sven J van der Lee, and Magda Tsolaki, and Frans R J Verhey, and Julius Popp, and Pablo Martinez-Lage, and Rik Vandenberghe, and Alberto Lleó, and José Luís Molinuevo, and Sebastiaan Engelborghs, and Yvonne Freund-Levi, and Lutz Froelich, and Kristel Sleegers, and Valerija Dobricic, and Simon Lovestone, and Johannes Streffer, and Stephanie J B Vos, and Isabelle Bos, and , and August B Smit, and Kaj Blennow, and Philip Scheltens, and Charlotte E Teunissen, and Lars Bertram, and Henrik Zetterberg, and Betty M Tijms
sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer's disease and associate with neuronal injury markers.
May 2016, EMBO molecular medicine,
Copied contents to your clipboard!