Combined measurement of thyroid and plasma homocysteic acid for detecting the severity of vascular dementia

BACKGROUND: Recent researches demonstrate that onset of cerebral infarction always accompanies with obvious changes of function of thyroid axis; while, high-homocysteic acidemia has been proved as one of risk factors of vascular dementia and Alzheimer disease. Meanwhile, it is found that level of plasma homocysteic acid is positive correlation with injured degrees of cognitive function and brain damage. OBJECTIVE: To observe the changes of function of thyroid and level of homocysteic acid among patients with vascular dementia and compare with those patients without dementia cerebral infarction. DESIGN: Randomized grouping and contrast observation. SETTING: Department of Neurology, People’s Hospital Affiliated to Yunyang Medical College, South China Hospital of Wuhan University. PARTICIPANTS: A total of 38 patients with vascular dementia were hospitalized in the Department of Neurology, People’s Hospital Affiliated to Yunyang Medical College from February 2004 to December 2005. All patients met the diagnostic criteria of the Fourth Edition of Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) established by American Psychiatric Association. Based on educational degrees, Mini-mental Status Examination (MMSE) was classified into illiteracy (≤ 17 points), education of primary school (educational duration ≤ 6 years, ≤ 24 points) and education of middle school or above (educational duration > 6 years, ≤ 24 points). Forty patients with non-dementia cerebral infarction were regarded as the control group and checked with CT examination. There were no significant differences of sex and age between the two groups. All patients and relatives were provided the consent. METHODS: Within 24 hours after hospitalization, patients with vascular dementia received MMSE scores, and the degrees were classified based on the scoring results: mild (20-24 points), moderate (10-19 points) and severe (below 10 points). Levels of thyroxine were measured with radioimmunodetection and content of homocysteic acid was measured with high performance liquid chromatogram (HPLC) electrochemical detection. MAIN OUTCOME MEASURES: Levels of homocysteic acid and thyroxine among patients with vascular dementia and non-dementia cerebral infarction. RESULTS: A total of 38 patients with vascular dementia and 40 patients with non-dementia cerebral infarction were involved in the final analysis. ① Levels of triiodothyronine (T3), thyroxine (T4) and free T3 (FT3) were (0.9±0.4) μg/L, (92.9±26.4) μg/L and (3.9±1.8) pmol/L in vascular dementia group respectively, which were higher than those in control group [(1.3±0.3) μg/L, (110.2±28.7) μg/L, (7.2±2.1) pmol/L, t =2.766 6-7.433 6, P < 0.01]; while, level of homocysteic acid was (29.57±7.12) μmol/L in vascular dementia group, which was higher than that in control group [(24.53±4.98) μmol/L, t =3.637 7, P < 0.01]. There were no significant differences of free T4 (FT4) and thyrotropic-stimulating hormone (TSH) between the two groups (P > 0.05). ② Levels of FT3 of patients with mild, moderate and severe vascular dementia were (1.0±0.2), (0.9±0.1) and (0.8±0.1) μg/L, respectively; levels of homocysteic acid were (26.52±4.84), (29.59±5.56) and (32.71±6.17) μmol/L, respectively. There were significant differences among patients at the three degrees of vascular dementia (F =3.59-32.4, P < 0.01). However, there were no significant differences of T4, FT4 and TSH among the three kinds of patients (P > 0.05). CONCLUSION: Levels of thyroxine of patients with vascular dementia decrease; however, levels of homocysteic acid increase. Therefore, the results can indirectly reflect severities of vascular dementia.

Ultrasensitive and point-of-care detection of plasma phosphorylated tau in Alzheimer’s disease using colorimetric and surface-enhanced Raman scattering dual-readout lateral flow assay

Phosphorylation of tau at Ser(396,404)(p-tau^(396,404))is one of the earliest phosphorylation events,plasma p-tau^(396,404) level appears to be a potentially promising biomarker of Alzheimer’s disease(AD).The low abundance and easy degradation of p-tau in the plasma make the lateral flow assay(LFA)a suitable choice for point-of-care detection of plasma p-tau^(396,404) levels.Herein,based on our screening of a pair of p-tau^(396,404)-specific antibodies,we developed a colorimetric and surface-enhanced Raman scattering(SERS)dual-readout LFA for the rapid,highly sensitive,robust detection of plasma p-tau^(396,404) levels.This LFA realized a detection limit of 60 pg/mL by the naked eye or 3.8 pg/mL by SERS without cross-reacting with other tau species.More importantly,LFA rapidly and accurately differentiated AD patients from healthy controls,suggesting that it has the potential for clinical point-of-care application in AD diagnosis.This dual-readout LFA has the advantages of simple operation,rapid,ultra-sensitive detection,providing a new way for early AD diagnosis and intervention,especially in primary and community AD screening.