Alzheimer's disease (AD) is currently diagnosed only via clinical assessments and confirmed by postmortem brain pathology. Biochemical and neuroimaging markers could facilitate diagnosis, predict AD progression from a pre-AD state of mild cognitive impairment (MCI), and be used to monitor efficacies of disease-modifying therapies. It is now clear that cerebrospinal fluid (CSF) levels of A beta 40, A beta 42, total tau and phosphorylated tau have diagnostic values in AD. Measurements of the above CSF markers in combination are useful in predicting the risk of progression from MCI to AD. Recent advances further support a notion that plasma A beta levels, expressed as an A beta 42/A beta 40 ratio, could also be of value. New potential biomarkers are emerging, and CSF or plasma marker profiles may eventually become part of the clinician's toolkit for accurate AD diagnosis and management. These biomarkers, along with clinical assessment, neuropsychological testing and neuroimaging could achieve a much higher diagnostic accuracy for AD and related disorders in the future.
Alzheimer Disease ; blood ; cerebrospinal fluid ; Amyloid beta-Peptides ; blood ; cerebrospinal fluid ; Biomarkers ; blood ; cerebrospinal fluid ; Cognition Disorders ; blood ; cerebrospinal fluid ; Humans ; tau Proteins ; blood ; cerebrospinal fluid

OBJECTIVETo study the changes of biomarkers in cerebrospinal fluid (CSF) in cerebral amyloid angiopathy (CAA) dementia and Alzheimer(')s disease.

METHODSLevels of amyloid protein β (Aβ42, Aβ40) and phosphorylated Tau-protein (P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.

RESULTSThe levels of Aβ42, Aβ40, and P-tau in CSF and ratio of Aβ42/Aβ40 were (660.4 ± 265.2) ng/L, (7111.0 ± 1033.4) ng/L, (71.8 ± 51.5) ng/L, and 0.077 ± 0.033, respectively in CAA dementia and (663.6 ± 365.6) ng/L, (5115.0 ± 2931.1) ng/L, (47.7 ± 38.8) ng/L, and 0.192 ± 0.140, respectively in Alzheimer's disease patients. There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers (all P>0.05).

CONCLUSIONMeasurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.

Aged ; Aged, 80 and over ; Amyloid beta-Peptides ; cerebrospinal fluid ; Apolipoproteins E ; genetics ; Biomarkers ; cerebrospinal fluid ; Cerebral Amyloid Angiopathy ; cerebrospinal fluid ; Dementia ; cerebrospinal fluid ; Humans ; Male ; tau Proteins ; cerebrospinal fluid

Human genetic prion diseases (gPrDs) are directly associated with mutations and insertions in the PRNP (Prion Protein) gene. We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020. Nineteen different subtypes were identified and gPrDs accounted for 10.9% of all diagnosed PrDs within the same period. Some subtypes of gPrDs showed a degree of geographic association. The age at onset of Chinese gPrDs peaked in the 50-59 year group. Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI) cases usually displayed clinical symptoms earlier than genetic Creutzfeldt-Jakob disease (gCJD) patients with point mutations. A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients. None of the E196A gCJD patients reported a family history. The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD (sCJD). EEG examination was not sensitive for gPrDs. sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients. CSF 14-3-3 positivity was frequently detected in gCJD patients. Increased CSF tau was found in more than half of FFI and T188K gCJD cases, and an even higher proportion of E196A and E200K gCJD patients. 63.6% of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC. GSS and FFI cases had longer durations than most subtypes of gCJD. This is one of the largest studies of gPrDs in East Asians, and the illness profile of Chinese gPrDs is clearly distinct. Extremely high proportions of T188K and E196A occur among Chinese gPrDs; these mutations are rarely reported in Caucasians and Japanese.
14-3-3 Proteins/cerebrospinal fluid* ; China ; Creutzfeldt-Jakob Syndrome/genetics* ; Humans ; Mutation/genetics* ; Prion Diseases/genetics* ; Prion Proteins/genetics* ; Prions/genetics* ; tau Proteins/cerebrospinal fluid*

Alzheimer's disease (AD), also called presenile dementia, is one of the most common neurodegenerative diseases in elderly people. The main pathological features of AD include senile plaques (SPs), neurofibrillary tangles (NFTs) and neuron loss. A biomarker is a characteristic that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Class biomarkers of AD such as Abeta and phosphorylated tau have been widely used in clinical diagnosis of AD patients. Recently, novel technologies like proteomics, genomics, and imaging techniques have expanded the role of a biomarker from early diagnosis to monitoring the progression of diseases and evaluating the response to various treatments. In this article, we will review the progress of various biomarkers of AD.
Adipokines ; cerebrospinal fluid ; Alzheimer Disease ; cerebrospinal fluid ; diagnosis ; diagnostic imaging ; metabolism ; Amyloid beta-Peptides ; cerebrospinal fluid ; Biomarkers ; analysis ; Chitinase-3-Like Protein 1 ; Fluorodeoxyglucose F18 ; Humans ; Lectins ; cerebrospinal fluid ; Peptide Fragments ; cerebrospinal fluid ; Phosphorylation ; Positron-Emission Tomography ; Presenilins ; analysis ; alpha 1-Antitrypsin ; blood ; tau Proteins ; cerebrospinal fluid

BACKGROUND AND PURPOSE: The level of 14-3-3 protein in the cerebrospinal fluid (CSF) is increased in Creutzfeldt-Jakob disease (CJD) patients, which has led to it being used as a clinical biomarker for the ante-mortem diagnosis of human prion diseases. However, the specificity of the 14-3-3 protein is less reliable for CJD diagnosis. Newly developed assays including real-time quaking-induced conversion (RT-QuIC) have made it possible to detect the PrPSc-like abnormal prion isoform with a high sensitivity in animal and human specimens that might contain a minute amount of PrP(Sc) due to in vitro prion replication. METHODS: This study applied a highly sensitive RT-QuIC assay using recombinant human PrP to detect PrP(Sc) in the CSF of 81 patients with sporadic CJD (sCJD) in Korea. RESULTS: RT-QuIC analysis of the CSF samples based on the expression levels of 14-3-3 and total tau proteins revealed positivity in 62 of 81 sCJD patients (sensitivity of 76.5%) but no positive results in the 100 non-CJD patients. CONCLUSIONS: The sensitivity of the RT-QuIC in this study was similar to that in some previous reports, and the specificity of RT-QuIC was higher than that of 14-3-3 in CSF, suggesting that RT-QuIC analysis can complement the weakness of the specificity of 14-3-3 for the diagnosis of sCJD. These results indicate that RT-QuIC might be very useful for the rapid and specific diagnosis of sCJD and provide a practical novel method for the ante-mortem diagnosis of human prion diseases.
14-3-3 Proteins ; Animals ; Cerebrospinal Fluid ; Complement System Proteins ; Creutzfeldt-Jakob Syndrome* ; Diagnosis* ; Humans ; Korea* ; Prion Diseases ; Sensitivity and Specificity ; tau Proteins

BACKGROUND: The described clinical characteristics of early-onset Alzheimer's disease (EOAD) are distinct from that of late-onset AD. We reported a patient with atypical EOAD. CASE REPORT: A 54-year-old, truck driver developed gradual visuospatial, language and calculation deficits for 3 months. The neuropsychological impairments were extensive. Brain MRI revealed asymmetric atrophy in left medial temporal lobe along with distinct widening of sylvian fissure. (18)F-florbetapir-positron emission tomography (PET) showed a high uptake in the cortex. Further, the profiles of cerebrospinal fluid (CSF) biomarker were compatible with AD. CONCLUSIONS: We diagnosed the patient as EOAD based on the result of biomarker study. Increased Abeta burden was identified through amyloid PET imaging and decreased CSF Abeta level. The high rise of CSF Tau proteins was in agreement with the patient's extensive and rapid cognitive decline. This case report demonstrates the importance of AD biomarker study in confronting early-onset dementia with atypical clinical presentation.
Alzheimer Disease* ; Amyloid ; Atrophy ; Brain ; Cerebrospinal Fluid ; Dementia* ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Motor Vehicles ; Positron-Emission Tomography ; tau Proteins ; Temporal Lobe

BACKGROUND: The purpose of this study was to evaluate the value of phosphorylated tau with epitopes threonine 181(p-tau181) in cerebrospinal fluid (CSF) for the differential diagnosis of Alzheimer's disease typed dementia from other type of dementia. METHODS: A systematic literature search was performed to identify studies on p-tau181. Two evaluators independently evaluated the quality of the ten studies using the Scottish Intercollegiate Guidelines Network (SIGN) tool. The literature review covered from October 27, 1946 to October 22, 2013, and eight domestic databases including KoreaMed and international databases including Ovid-MEDLINE, EMBASE, and Cochrane Library were used. Tau concentrations were compared to healthy controls and to subjects with Alzheimer's disease (AD) using random effect meta-analysis. Outcome measures were Cohen's delta, sensitivity and specificity. RESULTS: Finally, 8 studies (8 diagnostic evaluation studies) were identified to evaluate CSF p-tau181. The effectiveness of this test was evaluated based on diagnostic accuracy. The diagnostic accuracy for identifying AD by ELISA was high which revealed pooled sensitivity as 0.843 (95% CI 0.818-0.867), pooled specificity as 0.799(95% CI 0.768-0.828) and summary receiver operating characteristic area under the curve 0.9082+/-0.0236. CONCLUSIONS: CSF p-tau181 concentrations in other type of dementia are intermediate between controls and AD patients. Overlap between both controls and AD patients results in insufficient diagnostic accuracy, and the development of more specific biomarkers for these disorders is needed.
Alzheimer Disease* ; Biomarkers ; Cerebrospinal Fluid ; Dementia ; Diagnosis, Differential* ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Humans ; Outcome Assessment (Health Care) ; ROC Curve ; Sensitivity and Specificity ; tau Proteins ; Threonine