BIOMAT Database Logo BIOMAT Database Logo

The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer's disease: a longitudinal PET study. 2020

Rola Ismail, and Peter Parbo, and Lasse Stensvig Madsen, and Allan K Hansen, and Kim V Hansen, and Jeppe L Schaldemose, and Pernille L Kjeldsen, and Morten G Stokholm, and Hanne Gottrup, and Simon F Eskildsen, and David J Brooks
Department of Clinical Medicine, PET-Centre, Aarhus University, Aarhus, Denmark. rola.ismail@clin.au.dk.

BACKGROUND The aim of this longitudinal study was to assess with positron emission tomography (PET) the relationship between levels of inflammation and the loads of aggregated β-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease. METHODS Forty-three subjects with mild cognitive impairment (MCI) had serial 11C-PK11195 PET over 2 years to measure inflammation changes, and 11C-PiB PET to determine β-amyloid fibril load; 22 also had serial 18F-Flortaucipir PET to determine tau tangle load. Cortical surface statistical mapping was used to localise areas showing significant changes in tracer binding over time and to interrogate correlations between tracer binding of the tracers at baseline and after 2 years. RESULTS Those MCI subjects with high 11C-PiB uptake at baseline (classified as prodromal Alzheimer's disease) had raised inflammation levels which significantly declined across cortical regions over 2 years although their β-amyloid levels continued to rise. Those MCI cases who had low/normal 11C-PiB uptake at baseline but their levels then rose over 2 years were classified as prodromal AD with low Thal phase 1-2 amyloid deposition at baseline. They showed levels of cortical inflammation which correlated with their rising β-amyloid load. Those MCI cases with baseline low 11C-PiB uptake that remained stable were classified as non-AD, and they showed no correlated inflammation levels. Finally, MCI cases which showed both high 11C-PiB and 18F-Flortaucipir uptake at baseline (MCI due to AD) showed a further rise in their tau tangle load over 2 years with a correlated rise in levels of inflammation. CONCLUSIONS Our baseline and 2-year imaging findings are compatible with a biphasic trajectory of inflammation in Alzheimer's disease: MCI cases with low baseline but subsequently rising β-amyloid load show correlated levels of microglial activation which then later decline when the β-amyloid load approaches AD levels. Later, as tau tangles form in β-amyloid positive MCI cases with prodromal AD, the rising tau load is associated with higher levels of inflammation.

UI MeSH Term Description Entries
D007090 Image Interpretation, Computer-Assisted Methods developed to aid in the interpretation of ultrasound, radiographic images, etc., for diagnosis of disease. Image Interpretation, Computer Assisted,Computer-Assisted Image Interpretation,Computer-Assisted Image Interpretations,Image Interpretations, Computer-Assisted,Interpretation, Computer-Assisted Image,Interpretations, Computer-Assisted Image
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008137 Longitudinal Studies Studies in which variables relating to an individual or group of individuals are assessed over a period of time. Bogalusa Heart Study,California Teachers Study,Framingham Heart Study,Jackson Heart Study,Longitudinal Survey,Tuskegee Syphilis Study,Bogalusa Heart Studies,California Teachers Studies,Framingham Heart Studies,Heart Studies, Bogalusa,Heart Studies, Framingham,Heart Studies, Jackson,Heart Study, Bogalusa,Heart Study, Framingham,Heart Study, Jackson,Jackson Heart Studies,Longitudinal Study,Longitudinal Surveys,Studies, Bogalusa Heart,Studies, California Teachers,Studies, Jackson Heart,Studies, Longitudinal,Study, Bogalusa Heart,Study, California Teachers,Study, Longitudinal,Survey, Longitudinal,Surveys, Longitudinal,Syphilis Studies, Tuskegee,Syphilis Study, Tuskegee,Teachers Studies, California,Teachers Study, California,Tuskegee Syphilis Studies
D008297 Male Males
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
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
D016229 Amyloid beta-Peptides Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. Alzheimer beta-Protein,Amyloid Protein A4,Amyloid beta-Peptide,Amyloid beta-Protein,beta Amyloid,beta-Amyloid Protein,Alzheimer's ABP,Alzheimer's Amyloid Fibril Protein,Amyloid AD-AP,Amyloid Fibril Protein, Alzheimer's,Amyloid beta-Proteins,ABP, Alzheimer's,AD-AP, Amyloid,Alzheimer ABP,Alzheimer beta Protein,Alzheimers ABP,Amyloid AD AP,Amyloid beta Peptide,Amyloid beta Peptides,Amyloid beta Protein,Amyloid beta Proteins,Amyloid, beta,Protein A4, Amyloid,Protein, beta-Amyloid,beta Amyloid Protein,beta-Peptide, Amyloid,beta-Peptides, Amyloid,beta-Protein, Alzheimer,beta-Protein, Amyloid,beta-Proteins, Amyloid
D016874 Neurofibrillary Tangles Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) UBIQUITINS. As one of the hallmarks of ALZHEIMER DISEASE, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. Neurofibrillary Tangle,Tangle, Neurofibrillary,Tangles, Neurofibrillary

Related Publications

Rola Ismail, and Peter Parbo, and Lasse Stensvig Madsen, and Allan K Hansen, and Kim V Hansen, and Jeppe L Schaldemose, and Pernille L Kjeldsen, and Morten G Stokholm, and Hanne Gottrup, and Simon F Eskildsen, and David J Brooks
Distinct relationships of amyloid-beta and tau deposition to cerebral glucose metabolic networks in Alzheimer's disease.
January 2020, Neuroscience letters,
Rola Ismail, and Peter Parbo, and Lasse Stensvig Madsen, and Allan K Hansen, and Kim V Hansen, and Jeppe L Schaldemose, and Pernille L Kjeldsen, and Morten G Stokholm, and Hanne Gottrup, and Simon F Eskildsen, and David J Brooks
Altered filamin A enables amyloid beta-induced tau hyperphosphorylation and neuroinflammation in Alzheimer's disease.
January 2017, Neuroimmunology and neuroinflammation,
Rola Ismail, and Peter Parbo, and Lasse Stensvig Madsen, and Allan K Hansen, and Kim V Hansen, and Jeppe L Schaldemose, and Pernille L Kjeldsen, and Morten G Stokholm, and Hanne Gottrup, and Simon F Eskildsen, and David J Brooks
Staging tau pathology with tau PET in Alzheimer's disease: a longitudinal study.
September 2021, Translational psychiatry,
Rola Ismail, and Peter Parbo, and Lasse Stensvig Madsen, and Allan K Hansen, and Kim V Hansen, and Jeppe L Schaldemose, and Pernille L Kjeldsen, and Morten G Stokholm, and Hanne Gottrup, and Simon F Eskildsen, and David J Brooks
Relationships Between the Deposition of Amyloid-β and Tau Protein and Glymphatic System Activity in Alzheimer's Disease: Diffusion Tensor Image Study.
January 2022, Journal of Alzheimer's disease : JAD,
Rola Ismail, and Peter Parbo, and Lasse Stensvig Madsen, and Allan K Hansen, and Kim V Hansen, and Jeppe L Schaldemose, and Pernille L Kjeldsen, and Morten G Stokholm, and Hanne Gottrup, and Simon F Eskildsen, and David J Brooks
Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimer's disease and mild cognitive impairment.
December 2019, Human brain mapping,
Rola Ismail, and Peter Parbo, and Lasse Stensvig Madsen, and Allan K Hansen, and Kim V Hansen, and Jeppe L Schaldemose, and Pernille L Kjeldsen, and Morten G Stokholm, and Hanne Gottrup, and Simon F Eskildsen, and David J Brooks
Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease.
January 2018, NeuroImage. Clinical,
Rola Ismail, and Peter Parbo, and Lasse Stensvig Madsen, and Allan K Hansen, and Kim V Hansen, and Jeppe L Schaldemose, and Pernille L Kjeldsen, and Morten G Stokholm, and Hanne Gottrup, and Simon F Eskildsen, and David J Brooks
Longitudinal tau PET in ageing and Alzheimer's disease.
May 2018, Brain : a journal of neurology,
Rola Ismail, and Peter Parbo, and Lasse Stensvig Madsen, and Allan K Hansen, and Kim V Hansen, and Jeppe L Schaldemose, and Pernille L Kjeldsen, and Morten G Stokholm, and Hanne Gottrup, and Simon F Eskildsen, and David J Brooks
Alzheimer's disease: beta-Amyloid protein and tau.
November 2002, Journal of neuroscience research,
Rola Ismail, and Peter Parbo, and Lasse Stensvig Madsen, and Allan K Hansen, and Kim V Hansen, and Jeppe L Schaldemose, and Pernille L Kjeldsen, and Morten G Stokholm, and Hanne Gottrup, and Simon F Eskildsen, and David J Brooks
Alcohol and Alzheimer's Disease-Does Alcohol Dependence Contribute to Beta-Amyloid Deposition, Neuroinflammation and Neurodegeneration in Alzheimer's Disease?
March 2017, Alcohol and alcoholism (Oxford, Oxfordshire),
Rola Ismail, and Peter Parbo, and Lasse Stensvig Madsen, and Allan K Hansen, and Kim V Hansen, and Jeppe L Schaldemose, and Pernille L Kjeldsen, and Morten G Stokholm, and Hanne Gottrup, and Simon F Eskildsen, and David J Brooks
Alcohol and Alzheimer's Disease-Does Alcohol Dependence Contribute to Beta-Amyloid Deposition, Neuroinflammation and Neurodegeneration in Alzheimer's Disease?
March 2017, Alcohol and alcoholism (Oxford, Oxfordshire),
Copied contents to your clipboard!