CSF phosporylated TAU protein levels correlate with cerebral glucose metabolism assessed with PET in Alzheimer's disease

Ceravolo, Roberto; Borghetti, D.; Kiferle, Lorenzo; Tognoni, Gloria; Giorgetti, Alejandro; Neglia, Danilo; Sassi, Nadia; Frosini, Daniela; Rossi, Chiara; Petrozzi, Lucia; Siciliano, Gabriele; Murri, Luigi

doi:10.1016/j.brainresbull.2008.01.010

Cited by 44 publications

(24 citation statements)

References 27 publications

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“…A predominantly negative correlation with FDG PET confirms previous studies that had shown a similar correlation between FDG PET with phosphorylated tau in CSF [1].…”

supporting

confidence: 90%

Tau PET and tauopathies

Herholz

2016

Eur J Nucl Med Mol Imaging

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PET tracers for pathological deposits of tau protein aggregates in the brain are currently undergoing rapid development. They are targeting pathological deposits of tau aggregates, which are present in several neurodegenerative disorders, the socalled tauopathies. The most frequent of these is Alzheimer's disease, which is characterised by a combination of neurofibrillary tangles (primarily tau) and plaques (primarily beta-amyloid). However, pathological deposits of tau (without beta-amyloid plaques) also are present in rarer diseases, including progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), some types of frontotemporal dementia (FTD), and secondarily also in posttraumatic encephalopathy [2,12]. Most publications on PET tau imaging relate to Alzheimer's disease only, while a paper by Chiotis et al. in this issue also included a few cases of non-AD tauopathies.The paper should be considered within the background of the main clinical research needs and expectations for tau imaging. The most obvious ones are related to the potential of tau PET as an imaging biomarker in clinical trials of therapeutic compounds to delay the onset or progression of dementia in AD. Alternatively, increased levels of tau in CSF are also being used as a biomarker of pathological tau deposition in such trials. CSF sampling includes the option to also assess abnormal tau phosphorylation as well as other potential biomarkers, such as inflammatory cytokines [5]. Longitudinal studies will need to assess the merits of imaging the regional brain distribution of tau PET deposits compared to the analysis of their molecular diversity in CSF. Most importantly, a tau biomarker should measure disease progression at a prodromal stage where symptoms are absent or mild and do not show much change within typical trial durations. Tau PET could also help with accurate staging of prodromal AD, analogous to the pathological staging proposed and validated by Braak and Braak [10]. From a diagnostic perspective, tau PET would be expected to separate tauopathies from diseases associated with other pathological protein deposits such as Lewy bodies, TDP43, FUS, and prion protein [11], and to discriminate between different tauopathies by their regional distribution patterns [8].What does the paper by Chiotis et al. demonstrate? A main result is an excellent discrimination between healthy controls and AD patients. However, patients were relatively young with a maximum age of 74 years (whereas most AD patients are older) and the sample of controls was quite small and even younger, including only four elderly controls with a maximum age of 65. Thus, the study could not address the issue of discriminating between primary age-related tauopathy (PART), which also increases substantially with old age, and preclinical or prodromal AD. PART is characterised by mesial temporal tau deposits in the absence of beta-amyloid plaques and is usually regarded as a relatively benign age-related condition that is different from AD [6]. This issue has been add...

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“…A predominantly negative correlation with FDG PET confirms previous studies that had shown a similar correlation between FDG PET with phosphorylated tau in CSF [1].…”

supporting

confidence: 90%

Tau PET and tauopathies

Herholz

2016

Eur J Nucl Med Mol Imaging

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“…5,24 The variables used in our analyses were summary measures intended to reflect a global index for each tracer; our results cannot address the ROI differences in the patterns of relationships but do introduce the idea that diagnosis may be a confounding factor in these associations. Finally, the relationships between FDG-PET and CSF measures that have been previously reported are variable, with some studies suggesting an association between FDG and p-tau 14,25,26 but not A␤ 26 and other studies showing no association with p-tau but weak associations with t-tau. 27 These studies are difficult to compare because they used different subject groups, different imaging methods, different immunoassays, and different tau phosphorylation sites.…”

Section: Resultsmentioning

confidence: 90%

Relationships between biomarkers in aging and dementia

Jagust

Landau

Shaw³

et al. 2009

Neurology

424

341

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“…Interestingly, the APP level of the human cerebrospinal liquor shows a positive correlation with the progress of age independently from any illness [10]. Beside amyloid-β, neurofibrillary tangles (NFT) are other hallmarks of AD [11]. NFT production is a result of abnormal hyperphosphorylation of the microtubule-associated protein tau and the mitogen-activated protein kinase (MAPK) plays a leading role in this abnormal hyperphosphorylation [27].…”

Section: Introductionmentioning

confidence: 99%

Increase in Alzheimer's related markers preceeds memory disturbances: Studies in vasopressin-deficient Brattleboro rat

Várga

Klausz

Domokos

et al. 2014

Brain Research Bulletin

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Alzheimer's disease (AD) is the most common form of dementia in the elderly. For more effective therapy early diagnostic markers could be beneficial. Therefore we compared one year old rats with adults and examined if changes in possible brain markers of AD preceeded memory decline. We also tested if vasopressin-deficient animals were useful model of AD as vasopressin has well known positive effect on memory and AD patient has decreased vasopressin production.We compared adult (3 month) and old (12 month), normal and vasopressin-deficient Brattleboro rats. To receive a comprehensive picture about their memory we examined their social discrimination, object discrimination and conditioned learning abilities (shuttle box).Amyloid precursor protein (APP), mitogen-activated protein kinase 1 (MAPK1), β-actin and tryptophan 2,3-dioxygenase 2 (TDO2) mRNA levels was measured by quantitative PCR.There was no difference between the memory of adult and aged groups. The vasopressin-deficient rats at both ages showed a weaker performance in the course of social and object discrimination tests and a higher escape failure during the shuttle box experiment. The brain marker mRNAs of the elder animals were higher than the levels of the adults, but the absence of vasopressin had no influence on them.Thus, the one year old rats showed elevated levels of AD-related markers, but memory deficits were observable only in vasopressin deficient animals. Vasopressin does not seem to have pathogenic role in AD. Changes in the studied markers might predict later symptoms, although further studies are required for confirmation.

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CSF phosporylated TAU protein levels correlate with cerebral glucose metabolism assessed with PET in Alzheimer's disease

Cited by 44 publications

References 27 publications

Tau PET and tauopathies

Tau PET and tauopathies

Relationships between biomarkers in aging and dementia

Increase in Alzheimer's related markers preceeds memory disturbances: Studies in vasopressin-deficient Brattleboro rat

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