CSF APPsα and Phosphorylated Tau Protein Levels in Mild Cognitive Impairment and Dementia of Alzheimer's Type

Introduction The search for a reliable neuroimaging biomarker in Alzheimer’s disease is a matter of intense research. The presence of cerebral microbleeds seems to be a potential biomarker. However, it is not clear if the presence of microbleeds has clinical usefulness to differentiate mild Alzheimer’s disease and amnestic mild cognitive impairment from normal aging. We aimed to verify if microbleed prevalence differs among three groups: mild Alzheimer’s disease, amnestic mild cognitive impairment due to Alzheimer’s disease, and normal controls. Moreover, we studied whether microbleeds were associated with apolipoprotein E allele ɛ4 status, cerebrospinal fluid amyloid-beta, total and phosphorylated tau protein levels, vascular factors, and cognition. Methods Twenty-eight mild Alzheimer’s disease patients, 34 with amnestic mild cognitive impairment and 36 cognitively normal elderly subjects underwent: magnetic resonance imaging with a susceptibility-weighted imaging sequence on a 3T scanner, apolipoprotein E genotyping and a full neuropsychological evaluation. Only amnestic mild cognitive impairment and mild Alzheimer’s disease underwent cerebrospinal fluid analysis. We compared the groups and verified if microbleeds were predicted by all other variables. Results Mild Alzheimer’s disease presented a higher prevalence of apolipoprotein E allele ɛ4 in relation to amnestic mild cognitive impairment and control group. No significant differences were found between groups when considering microbleed presence. Logistic regression tests failed to find any relationship between microbleeds and the variables. We performed three different regression models using different independent variables: Model 1 - amyloid-beta, phosphorylated tau protein, total tau, apolipoprotein E allele ɛ4 status, age, and sex; Model 2 - vascular risk factors, age, and sex; Model 3 - cognitive scores sex, age, and education. Conclusion Although microbleeds might be related to the Alzheimer’s disease process, their presence is not a good candidate for a neuroimaging biomarker of the disease, especially in its early phases.

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Adult‐onset neuronal intranuclear inclusion disease showing markedly high phosphorylated tau protein levels in cerebrospinal fluid

Geriatrics and Gerontology International ◽

10.1111/ggi.13964 ◽

2020 ◽

Vol 20 (8) ◽

pp. 793-795

Author(s):

Shuntaro Serisawa ◽

Kentaro Hirao ◽

Tomohiko Sato ◽

Yusuke Ogawa ◽

Hidekazu Kanetaka ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Tau Protein ◽

Phosphorylated Tau ◽

Adult Onset ◽

Intranuclear Inclusion ◽

Protein Levels ◽

Neuronal Intranuclear Inclusion ◽

Phosphorylated Tau Protein

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Comparison of Neuronal and Axonal Degeneration Markers Cystatin-C, Beta-Amyloid (1-42), Total and Phosphorylated Tau Protein Levels in Cerebrospinal Fluids of Patients with Multiple Sclerosis and Alzheimer’s Disease

Niche Journal ◽

10.5152/niche.2012.06 ◽

2013 ◽

Vol 1 (2) ◽

pp. 24-30

Author(s):

Hulya Akdeniz ◽

Zeynep Ginis ◽

Selcuk Comoglu ◽

Bilge Kocer ◽

Ferda Pinarli ◽

...

Keyword(s):

Multiple Sclerosis ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cystatin C ◽

Tau Protein ◽

Axonal Degeneration ◽

Beta Amyloid ◽

Phosphorylated Tau ◽

Protein Levels ◽

Phosphorylated Tau Protein

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Flavonoids from Stem and Leaf of Scutellaria Baicalonsis Georgi Inhibit the Phosphorylation on Multi-sites of Tau Protein Induced by Okadaic Acid and the Regulative Mechanism of Protein Kinases in Rats

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200901101233 ◽

2020 ◽

Vol 23 ◽

Author(s):

Yang Gao ◽

Xiao-Qing Wang ◽

Shuai Ma ◽

Yong-Cai Dong ◽

Ya-Zhen Shang

Keyword(s):

Cerebral Cortex ◽

Protein Kinases ◽

Okadaic Acid ◽

Tau Protein ◽

Memory Impairment ◽

Phosphorylated Tau ◽

Successful Model ◽

Protein Levels ◽

Regulative Mechanism ◽

Phosphorylated Tau Protein

Aim: The aim of the present study is to investigate the effect of flavonoids from stem and leaf of Scutellaria baicalonsis Georgi (SSF) on multi-sites phosphorylation of tau protein in cerebral cortex and hippocampus of rats induced by okadaic acid (OA) and the regulative mechanism of the protein kinases. Methods: The model of AD-like memory impairment and neuronal injuries was established in male SD rats who were microinjected with OA (200 ng/kg) to establish a memory impairment model and screened for successful model rats by Morris water maze on day 21 after surgery. The successful model rats were continuously administered with intragastric infusion (ig) SSF 25, 50, and 100 mg/kg or Ginkgo biloba leaves flavonoids (GLF) 200 mg/kg for 36 d. The relative protein expressed levels of phosphorylated tau protein at sites of Ser199, Ser202, Ser214, Ser404 and Thr231, protein kinases (CDK5, PKA, pTyr216-GSK3β and pSer9-GSK3β) were detected by Western blotting. Results: The relative protein expressed levels of p-tau(Ser199), p-tau(Ser202), p-tau(Ser214), p-tau(Ser404) p-tau(Thr231), and pTyr216-GSK3β were significantly increased in both cerebral cortex and hippocampus regions of the model rats subjected to intracerebroventricular injection of OA (P<0.01), while the protein expressed levels of CDK5, PKA and pSer9- GSK3β (P<0.01) were reduced. SSF can dramatically reverse these increments in phosphorylated tau protein levels (P<0.01) and differently regulate the protein expressed levels of CDK5, PKA, and GSK3β (P<0.01) in rats’ cerebral cortex and hippocampus induced by OA. GLF also exhibits a similar effect on SSF. Conclusion: The results demonstrated that SSF could inhibit the hyperphosphorylation of tau in rats’ cerebral cortex and hippocampus induced by microinjection of OA, which may be related to the activities of protein kinase CDK5, PKA, and GSK3β.

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The role of proportion of cerebrospinal fluid total Tau-protein and phosphorylated Tau-protein levels in differential diagnosis of CJD

European Psychiatry ◽

10.1016/j.eurpsy.2008.01.312 ◽

2008 ◽

Vol 23 ◽

pp. S198

Author(s):

M. Valis ◽

J. Hort ◽

J. Masopust ◽

R. Talab

Keyword(s):

Cerebrospinal Fluid ◽

Differential Diagnosis ◽

Tau Protein ◽

Phosphorylated Tau ◽

Protein Levels ◽

Total Tau ◽

Phosphorylated Tau Protein

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Phosphorylated tau protein as a core biomarker of Alzheimer’s disease

Pharmacopsychiatry ◽

10.1055/s-2003-825356 ◽

2004 ◽

Vol 36 (05) ◽

Author(s):

H Hampel

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Tau Protein ◽

Phosphorylated Tau ◽

Phosphorylated Tau Protein

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DEF8 and Autophagy-Associated Genes are Altered in Mild Cognitive Impairment, Probable Alzheimer’s Disease Patients and a Transgenic Model of the Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-201264 ◽

2021 ◽

pp. 1-16

Author(s):

Esteban Leyton ◽

Diego Matus ◽

Sandra Espinoza ◽

José Matías Benitez ◽

Bastián I. Cortes ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Real Time ◽

Real Time Pcr ◽

Mononuclear Cells ◽

Differentially Expressed ◽

Protein Levels ◽

5Xfad Mice

Background: Disturbances in the autophagy/endolysosomal systems are proposed as early signatures of Alzheimer’s disease (AD). However, few studies are available concerning autophagy gene expression in AD patients. Objective: To explore the differential expression of classical genes involved in the autophagy pathway, among them a less characterized one, DEF8 (Differentially expressed in FDCP 8), initially considered a Rubicon family member, in peripheral blood mononuclear cells (PBMCs) from individuals with mild cognitive impairment (MCI) and probable AD (pAD) and correlate the results with the expression of DEF8 in the brain of 5xFAD mice. Method: By real-time PCR and flow cytometry, we evaluated autophagy genes levels in PBMCs from MCI and pAD patients. We evaluated DEF8 levels and its localization in brain samples of the 5xFAD mice by real-time PCR, western blot, and immunofluorescence. Results: Transcriptional levels of DEF8 were significantly reduced in PBMCs of MCI and pAD patients compared with healthy donors, correlating with the MoCA and MoCA-MIS cognitive tests scores. DEF8 protein levels were increased in lymphocytes from MCI but not pAD, compared to controls. In the case of brain samples from 5xFAD mice, we observed a reduced mRNA expression and augmented protein levels in 5xFAD compared to age-matched wild-type mice. DEF8 presented a neuronal localization. Conclusion: DEF8, a protein proposed to act at the final step of the autophagy/endolysosomal pathway, is differentially expressed in PBMCs of MCI and pAD and neurons of 5xFAD mice. These results suggest a potential role for DEF8 in the pathophysiology of AD.

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