OBJECTIVETo observe the correlation between the decline of cognitive function and the level of plasma homocysteine in patients with Alzheimer's disease (AD).

METHODSThirty six AD patients were selected from hospitals in Tianjin. The enrolled patients were in accord with the diagnosis criteria. Thirty two control subjects were corresponding patients without AD in the period. Blood samples were extracted from each subject to determine the levels of homocysteine (Hcy) and folate. Cognitive status was evaluated by the mini- mental state examination (MMSE) and clinical dementia rating scale (CDR).

RESULTSThe mean value of serum Hcy concentration [(17.51 +/- 5.62) micromol/L] of AD group was higher than that of control group [(12.38 +/- 4.25)micromol/L]. The serum [(5.17 +/- 1.76) microg/L] and diet folate [(206.94 +/- 44.51) microg/d] concentration of AD group were lower than those of control group [(7.92 +/- 2.22) microg/L, (259.74 +/- 41.92) microg/ d]. The incidence of hyperhomocysteinemia in AD group (64%) was higher than that in control group (22%). A significant relation between Hcy concentrations and the CDR was observed. With the increase of Hcy concentrations the CDR raised, and with the increase of Hcy concentrations the MMSE decreased.

CONCLUSIONHyperhomocysteinemia is one of the risk factors inducing the onset of AD. There is a significant negative correlation between Hcy levels and cognitive levels in AD group. Folate deficiency is an important reason to cause elevated Hcy levels in AD.

Alzheimer Disease ; blood ; etiology ; Case-Control Studies ; Folic Acid ; blood ; Homocysteine ; blood ; Humans ; Hyperhomocysteinemia ; blood ; complications

OBJECTIVETo investigate serum adiponectin level in patients with Alzheimer's disease (AD) and its correlation with the patients' cognitive function.

METHODSThis case-control study was conducted in 90 patients with a highly probable diagnosis ofAD, who were divided into mild, moderate and severe group saccording to the MMSE score. Ninety healthy subjects matched for age and gender with the AD patients were selected as the control group. The serum levels ofadiponectin in the participants were detected using enzyme-linked immunosorbent assay.

RESULTSSerum adiponectin level was significantly lower in the AD group than in the control group (P<0.05). Of the 3 subgroups of the AD patients, the moderate and severe AD groups showed significantly lower serum adiponectin level sthan the control group (P<0.05), but the difference in adiponectin levels was not significant between the mild AD group and the control group (P>0.05); serum adiponectin levels also differed significantly among the 3 subgroups of AD patients (P<0.05). Serum adiponectin level was positively correlated with the MMSE score in the AD patients (r=0.683, P<0.001).

CONCLUSIONSerum adiponectin levels are reduced in AD patients and associated with the degree of cognitive impairment.

Adiponectin ; blood ; Alzheimer Disease ; blood ; Case-Control Studies ; Cognition ; Cognitive Dysfunction ; blood ; Enzyme-Linked Immunosorbent Assay ; Humans

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β proteins (Aβ). In this study we explored the correlation of plasma Aβ40 and Aβ42 concentrations with Aβ42, total tau (tTau) and phosphorylated tau 181 (pTau181) levels in cerebrospinal fluid (CSF) in AD and control subjects to further understand the characteristics of plasma Aβ proteins levels. METHODS: The consecutive subjects (44 AD and 47 controls) in this study were recruited. The plasma levels of Aβ40 and Aβ42 were measured using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kits. And the corresponding CSFs were analyzed in terms of Aβ42, tTau and pTau181 concentrations using INNOTEST ELISA kits. Further, the albumin levels were measured both in serum and CSF and albumin ratio was obtained to check the integrity of blood-brain barrier. RESULTS: CSF Aβ42 concentrations were significantly decreased while tTau and pTau181 levels were significantly increased in AD subjects. The plasma levels of Aβ42 were significantly lower (p=0.007), while the Aβ40/Aβ42 ratio was significantly higher (p<0.001) in AD patients than in controls. The overall plasma Aβ42 levels showed a positive correlation with those of CSF Aβ42 (p=0.001), but not with the others in CSF. In subgroup analysis, the CSF Aβ42 demonstrated positive correlation with not only plasma Aβ42 but also Aβ40 levels in controls. However, no significant relationship was noted between plasma and CSF Aβ proteins in AD group. CONCLUSIONS: The plasma Aβ42 and Aβ40 concentrations were shown to have a close relationship with CSF Aβ42 levels in controls, but not in AD subjects. Our results suggest that the correlation between plasma Aβ40 and CSF Aβ42 levels is perturbed in AD.
Alzheimer Disease* ; Biomarkers* ; Blood-Brain Barrier ; Cerebrospinal Fluid* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Plasma* ; Statistics as Topic*

Imaging distribution of beta-amyloid plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the beta-amyloid plaques includes using radiolabeled peptides which can be only applied for peripheral beta-amyloid plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging beta-amyloid plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for beta-amyloid imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for beta-amyloid imaging agent.
Alzheimer Disease ; Blood-Brain Barrier ; Brain ; Congo Red ; Diagnosis ; Half-Life ; Peptides

BACKGROUND AND PURPOSE: Neuropsychiatric symptoms (NPS) such as anxiety, depression, and delusions affect up to 90% of all patients with Alzheimer's disease (AD). NPS is associated with significant caregiver burden and patient distress. Given the severe burden of NPS in AD, it is critical to know potential modifiable risk factors of NPS in AD. This study explores the association between hypertension and NPS in patients with drug-naïve AD. METHODS: We reviewed medical records of 149 patients with AD with (n=80) and without (n=69) hypertension. NPS were assessed using the Korean version of Neuropsychiatric Inventory (K-NPI). Affective, psychotic, and behavior symptom clusters were assessed separately. RESULTS: The total score of K-NPI was not significantly different between patients with AD with and without hypertension. Among K-NPI domains, scores of depression/dysphoria (p=0.045), anxiety (p=0.022), and apathy/indifference (p=0.037) were significantly higher in patients with AD with hypertension. Systolic blood pressure (BP) was associated with higher total K-NPI and affective symptom cluster scores. Diastolic BP was associated with affective symptom cluster scores. CONCLUSIONS: Results suggest that hypertension increases risk of specific NPS in patients with AD. Among NPS, hypertension was associated with affective symptom cluster.
Affective Symptoms ; Alzheimer Disease* ; Anxiety ; Blood Pressure ; Caregivers ; Delusions ; Depression ; Humans ; Hypertension* ; Medical Records ; Risk Factors

Cerebrospinal fluid (CSF) can provide vital informative about pathological processes occurring in the brain. In particular, the CSF concentrations of Abeta42, tTau, and pTau181 are useful for the early diagnosis of Alzheimer's disease (AD). However, many studies have demonstrated that confounding factors related to the preanalytical processing of CSF can seriously influence measurements of these AD biomarkers. It is therefore important to develop a standardized protocol for the acquisition and handling of CSF, particularly with regard to the types of tube used for collection and storage, the proper aliquot volume, blood contamination, and the number of tube transfers and freeze-thaw cycles, because these aspects of the procedure have been shown to affect AD biomarker measurements. A survey of the impact of several individual preanalytical procedures on the measurement of AD biomarkers in CSF was conducted for this review article, and the implications of the differences among them are discussed. Furthermore, following a review of the procedures used in Korean and international biomarker laboratories, a consensus was reached among a cooperative Korean multicenter research group regarding a standardized protocol for the analysis of AD biomarkers in CSF. All efforts were made to be stringent regarding the controversial issues associated with this protocol, thus minimizing the confounding influence of various factors on current investigations using established AD biomarkers and on future studies using novel biomarkers of AD and other neurodegenerative disorders.
Alzheimer Disease* ; Biomarkers* ; Blood Volume ; Brain ; Cerebrospinal Fluid* ; Consensus* ; Early Diagnosis ; Korea ; Neurodegenerative Diseases ; Pathologic Processes

The concept of the glial-vascular unit (GVU) was raised recently to emphasize the close associations between brain cells and cerebral vessels, and their coordinated reactions to diverse neurological insults from a "glio-centric" view. GVU is a multicellular structure composed of glial cells, perivascular cells, and perivascular space. Each component is closely linked, collectively forming the GVU. The central roles of glial and perivascular cells and their multi-level interconnections in the GVU under normal conditions and in central nervous system (CNS) disorders have not been elucidated in detail. Here, we comprehensively review the intensive interactions between glial cells and perivascular cells in the niche of perivascular space, which take part in the modulation of cerebral blood flow and angiogenesis, formation of the blood-brain barrier, and clearance of neurotoxic wastes. Next, we discuss dysfunctions of the GVU in various neurological diseases, including ischemic stroke, spinal cord injury, Alzheimer's disease, and major depression disorder. In addition, we highlight the possible therapies targeting the GVU, which may have potential clinical applications.
Humans ; Neuroglia ; Nervous System Diseases ; Blood-Brain Barrier ; Alzheimer Disease ; Glymphatic System

Accumulated evidence suggests that sporadic cases of Alzheimer's disease (AD) make up more than 95% of total AD patients, and diabetes has been implicated as a strong risk factor for the development of AD. Diabetes shares pathological features of AD, such as impaired insulin signaling, increased oxidative stress, increased amyloid-beta (Aβ) production, tauopathy and cerebrovascular complication. Due to shared pathologies between the two diseases, anti-diabetic drugs may be a suitable therapeutic option for AD treatment. In this article, we will discuss the well-known pathologies of AD, including Aβ plaques and tau tangles, as well as other mechanisms shared in AD and diabetes including reactive glia and the breakdown of blood brain barrier in order to evaluate the presence of any potential, indirect or direct links of pre-diabetic conditions to AD pathology. In addition, clinical evidence of high incidence of diabetic patients to the development of AD are described together with application of anti-diabetic medications to AD patients.
Alzheimer Disease ; Blood-Brain Barrier ; Encephalitis ; Humans ; Incidence ; Insulin ; Neuroglia ; Oxidative Stress ; Pathology ; Risk Factors ; Tauopathies

BACKGROUND: Abnormal platelet activation has been identified in several disorders characterizedby vascular patholo-gy including coronary artery disease, Alzheimer disease, myeloproliferative disorders, diabetes, preeclampsia, inflam-matory bowel disease and glomerular disease. Antiplatelet therapy has been valuable in the management of some of these conditions. The aim of this study is to verify usefulness of mean platelet component (MPC) concentration as a marker of thrombotic process in patients with cerebral infarction. Our hypothesis is that MPC as measured by the ADVIA(R) 120 hematology system is used to detect and monitor platelet activation associated with thrombotic process of ischemic stroke. METHODS: To study the existence of platelet activation at the onset of cerebral infarction, mean platelet concentration of platelets were measured daily during post-stroke 10 days. Thirty-four acute thrombotic cerebral infarction and seventeen age-matched healthy persons were selected for this study. To investigate the time course of the platelet MPC changes observed in stroke patients, the blood samplings for MPC measuring were done and analyzed on the ADVIA 120(R) system. RESULTS: There was a statistically significant decrease in MPC concentration of the platelets at post-stroke 3rd to 7th day compared to the control group ( p < 0.05). CONCLUSIONS: We conclude that a reduction of MPC as measured by the ADVIA 120(R) hematology system may be used to detect and monitor thrombotic process associated with platelet activation in ischemic stroke.
Alzheimer Disease ; Blood Platelets* ; Cerebral Infarction ; Coronary Artery Disease ; Hematology ; Humans ; Myeloproliferative Disorders ; Platelet Activation* ; Pre-Eclampsia ; Stroke*

Alzheimer's disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD. In this review, we summarize the latest achievements, including diagnostic biomarkers, polygenic hazard score, amyloid and tau PET imaging, clinical trials targeting amyloid-beta (Aβ), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.
Alzheimer Disease ; diagnosis ; physiopathology ; therapy ; Animals ; Biomarkers ; blood ; Biomedical Research ; methods ; Disease Progression ; Humans ; Magnetic Resonance Imaging