Correlation of blood pressure levels at different time periods throughout the day with total CSVD burden and MRI imaging markers.

Purpose: Hypertension is an important risk factor for atherosclerotic cerebral small vessel disease (CSVD). Higher blood pressure is associated with a higher CSVD burden and the presence of relevant magnetic resonance imaging (MRI) markers. However, the effect of blood pressure level on CSVD burden and imaging markers including white matter hyperintensity (WHM), lacune, enlarged perivascular spaces (EPVS), and cerebral microbleed (CMB) remains unknown. The purpose of this study was to investigate the correlation between blood pressure level and CSVD burden at different time periods throughout the day. Methods: In total, 144 in-patients with CSVD (66.4 ± 9.8 years, 50% male) were enrolled and underwent brain MRI, and 24-h ambulatory blood pressure was assessed. Patients were categorized into five groups according to their MRI-evaluated total CSVD burden scores (0-4). Spearman's correlation analysis was performed to examine the correlation between blood pressure levels at different time periods and the total CSVD score or the markers of periventricular WMH, deep WMH, lacune, EPVS, and CMB. Results: Of the 144 patients, 83.3% (120/144) harbored one or more CSVD markers of interest. The systolic blood pressure (SBP) of 24-h, daytime, nighttime, and morning differed significantly among the five groups. The SBP levels increased significantly with the total CSVD scores during 24 h (P = 0.018), daytime (P = 0.018), and nighttime (P = 0.035). Spearman's correlation analysis demonstrated that the SBP of 24 h, daytime, nighttime, and morning and the diastolic blood pressure (DBP) of 24 h and morning positively and significantly correlated with the total CSVD score (P < 0.05). A logistic regression analysis indicated that both morning SBP and DBP were independent risk factors for total CSVD burden (OR = 1.13, 95% CI: 1.02-1.23, P = 0.015; OR = 1.19, 95% CI: 1.06-1.33, P = 0.005). Spearman's correlation analysis indicated a significant positive correlation between morning SBP and higher deep WMH Fazekas score (r = 0.296, P < 0.001), EPVS grade in the basal ganglia (r = 0.247, P = 0.003), and the presence of lacune (r = 0.173, P = 0.038) and CMB (r = 0.326, P < 0.001). Morning DBP only correlated positively with the presence of CMB (r = 0.292, P < 0.001). Conclusion: Higher SBP signficantly correlated with total CSVD burden in patients with atherosclerotic CSVD. Early morning blood pressure level is an important indicator to reflect the severity of CSVD patients.

Mortality of Alzheimer's Disease and Other Dementias in China: Past and Future Decades.

Objectives: This study aimed to explore the distribution features and trends of dementia mortality in China from 2011 to 2020 and make a prediction for the next decade. Methods: Mortality-relevant data were gathered from the Chinese Center for Disease Control and Prevention's Disease Surveillance Points system. Joinpoint regression was applied to evaluate the trends. Results: Crude Mortality Rate (CMR) of AD and other dementias increased from 3.7 per 100,000 to 6.2 per 100,000 in 2011-2020, with an Average Annual Percent Change (AAPC) of 5.3% (95% CI 4.4%-6.3%). Age-Standardized Mortality Rate (ASMR) slightly decreased from 5.0 per 100,000 to 4.1 per 100,000 in 2011-2020, with AAPC of -0.4% (95% CI -2.5%-1.8%). CMR will increase to 9.66 per 100,000 while ASMR will decline to 3.42 per 100,000 in the following decade. Conclusion: The upward trend in CMR and downward trend in ASMR suggested the further development of population aging and dementia mortality in the past and future decades. In China, there were gender, urban-rural, regional and age differences.

Mild hyperphenylalaninemia (hpa) presenting as orthostatic tremor: a case report.

BACKGROUND: Orthostatic tremor (OT) is a type of postural tremor of the lower extremities that has not been described in either phenylketonuria (PKU) or hyperphenylalaninemia (HPA). Because little is known about the clinical features and therapeutic responses of OT in mild HPA, we describe a mild HPA patient who presented with OT as an initial symptom. CASE PRESENTATION: A 22-year-old male was admitted for bilateral leg tremor while standing, with symptom onset eight months prior. One month before admission, the tremor disappeared in the left leg but persisted in the right leg. Electromyography recorded from the right gastrocnemius revealed a 6-8 Hz tremor, which appeared when the patient was standing and disappeared when he was resting or walking. Blood screening showed a phenylalanine/tyrosine ratio of 2.06 and a phenylalanine level of 140 µmol/L. Urine metabolic screening was negative. Whole-exome sequencing confirmed the presence of a compound heterozygous mutation, c.158G > A and c.728G > A, in phenylalanine hydroxylase (PAH) gene. After three months of levodopa/benserazide tablets (250 mg, tid) and a low-phenylalanine diet treatment, the tremor disappeared. CONCLUSIONS: Young-onset mild HPA is a relatively rare autosomal recessive metabolic disease, and slow OT is a rare clinical feature. Metabolic screening and genetic testing are the keys to early diagnosis and treatment. For adolescents and young adults, appropriate medication and long-term dietary therapy remain important treatments. This case expanded the disease spectrum of slow OT.

Discovery and function exploration of microRNA-155 as a molecular biomarker for early detection of breast cancer.

BACKGROUND: MicroRNA-155 (miR-155) may function as a diagnostic biomarker of breast cancer (BC). Nevertheless, the available evidence is controversial. Therefore, we performed this study to summarize the global predicting role of miR-155 for early detection of BC and preliminarily explore the functional roles of miR-155 in BC. METHODS: We first collected published studies and applied the bivariate meta-analysis model to generate the pooled diagnostic parameters of miR-155 in diagnosing BC such as sensitivity, specificity and area under curve (AUC). Then, we applied function enrichment and protein-protein interactions (PPI) analyses to explore the potential mechanisms of miR-155. RESULTS: A total of 21 studies were finally included. The results indicated that miR-155 allowed for the discrimination between BC patients and healthy controls with a sensitivity of 0.87 (95% CI 0.78-0.93), specificity of 0.82 (0.72-0.89), and AUC of 0.91 (0.88-0.93). In addition, the overall sensitivity, specificity and AUC for circulating miR-155 were 0.88 (0.76-0.95), 0.83 (0.72-0.90), and 0.92 (0.89-0.94), respectively. Function enrichment analysis revealed several vital ontologies terms and pathways associated with BC occurrence and development. Furthermore, in the PPI network, ten hub genes and two significant modules were identified to be involved in some important pathways associated with the pathogenesis of BC. CONCLUSIONS: We demonstrated that miR-155 has great potential to facilitate accurate BC detection and may serve as a promising diagnostic biomarker for BC. However, well-designed cohort studies and biological experiments should be implemented to confirm the diagnostic value of miR-155 before it can be applied to routine clinical procedures.

Increased cerebrospinal fluid neurofilament light chain in central nervous system inflammatory demyelinating disease.

BACKGROUND: Central nervous system (CNS) inflammatory demyelinating disease (IDD) is an immune-mediated disease that is pathologically characterized by demyelination and inflammatory infiltration in the CNS and includes clinically isolated syndrome (CIS), multiple sclerosis (MS), and neuromyelitis optica spectrum disorders (NMOSD). IDD is usually characterized by variable symptoms, multivariate imaging, uncertain reactions to treatment, and a variable prognosis, which makes it difficult to diagnose early. In recent years, the role of the neurofilament light chain (NFL), an axonal injury biomarker, in IDD has become increasingly important. We will detect and analyse cerebrospinal fluid (CSF) NFL levels in IDD and normal control patients to determine the significance of NFL in the diagnosis and prognostic prediction of IDD. METHODS: A total of 41 CIS, 34 MS and 73 NMOSD patients and 40 other patients with conditions such as neurosis and migraine with lumbar puncture were enrolled as the patient groups and the normal control (NC) group from the population of in- and outpatients of the Department of Neurology of the Sixth Medical Centre of Chinese People's Liberation Army General Hospital from January 2014 to October 2016. Clinical and neuroimaging features of the patient groups as well as CSF samples from both types of groups were collected, and the NFL levels of CSF were measured by enzyme linked immunosorbent assay. RESULTS: CSF NFL levels in the CIS, MS and NMOSD groups were significantly higher than those in the NC group (P < 0.05, analysis of variance of NFL levels was performed after logarithmic transformation based on 10). There were no statistically significant differences in the CSF NFL levels among the CIS, MS and NMOSD groups (P > 0.05). The NFL levels of CSF in the CIS, MS and NMOSD groups were correlated with the expanded disability status scale score and enhancement in gadolinium-magnetic resonance imaging (all P < 0.05). Gender, oligoclonal band in CSF, aquaporin 4 antibody and 25­hydroxy vitamin D3 [25(OH)D3] in serum were not related to the NFL levels (P > 0.05). CONCLUSION: The NFL level of CSF is conducive to assessing the severity and probable progress of IDD but is not helpful in distinguishing IDD among Chinese.

Vascular endothelial growth factor improves the cognitive decline of Alzheimer's disease via concurrently inducing the expression of ADAM10 and reducing the expression of ß-site APP cleaving enzyme 1 in Tg2576 mice.

Alzheimer's disease (AD) is primarily characterized by the production and deposit of ß-amyloid protein (Aß) in ß-amyloid plaques (APs). On this basis, we investigated whether vascular endothelial growth factor (VEGF), a growth factor with important neuroprotective activity, may provide a therapeutic opportunity for treating AD. We initially found that the expression and production of VEGF was downregulated in the brains of Tg2576 mice during the course of AD development and progression. Restoring VEGF in the brains of Tg2576 mice antagonized the production and deposit of Aß in Tg2576 mice. The addition of VEGF concurrently increased the expression of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and decreased the expression of ß-site APP cleaving enzyme 1 (BACE1), which contributes to the enhanced clearance of Aß in vivo. By decreasing the production and deposit of Aß, VEGF improved the cognitive decline of Tg2576 mice. These observations provide a novel implication for VEGF as a therapeutic approach for the treatment of AD.

PGC-1α or FNDC5 Is Involved in Modulating the Effects of Aß1-42 Oligomers on Suppressing the Expression of BDNF, a Beneficial Factor for Inhibiting Neuronal Apoptosis, Aß Deposition and Cognitive Decline of APP/PS1 Tg Mice.

Alzheimer's disease (AD) is generally defined as the aberrant production of ß-amyloid protein (Aß) and hyperphosphorylated tau protein, which are deposited in ß-amyloid plaques (APs) and neurofibrillary tangles (NFTs), respectively. Decreased levels of brain-derived neurotrophic factor (BDNF) have been detected in patients with AD compared to control subjects. However, the underlying molecular mechanisms driving the downregulation of the BDNF remain unknown. Therefore, we explored the mechanisms underlying the regulation of BDNF in the neurons of APP/PS1 transgenic (Tg) mice, an AD experimental model. Using the APP/PS1 Tg mice, we found that BDNF expression was markedly downregualted at the age of 3- and 9-month-old. After cerebroventricular injection (i.c.v) of Aß1-42 oligomers into the mice, BDNF was also found to be decreased, which demonstrated the critical roles of the Aß1-42 oligomers in regulating the expression of BDNF. In neuronal culture, peroxisome proliferators-activated receptor γ coactivator 1α (PGC-1α) and fibronectin type III domain-containing 5 (FNDC5) were found to be downregulated by treatment with the Aß1-42 oligomers. In addition, overexpression of either PGC-1α or FNDC5 reversed the suppressive effects of the Aß1-42 oligomers on the expression of BDNF in neuroblastoma 2a (n2a) cells. More importantly, elevating the levels of PGC-1α, FNDC5 or BDNF in the n2a cells counteracted the effects of the Aß1-42 oligomers on neuronal apoptosis. Additionally, intranasal administration BDNF in the APP/PS1 Tg mice decreased the Aß deposition and reduced the cognitive decline of the mice.

[Analysis of serum lipid level in patients with multiple system atrophy].

OBJECTIVE: To explore the serum levels of lipids and lipoproteins in patients with multiple system atrophy (MSA). METHODS: From July 2009 to June 2014, a total of 62 MSA patients from the neurology department of our hospital were enrolled as the case group and 63 healthy individuals were enrolled as control group. The serum levels of lipids and lipoproteins were compared between two groups and also analyzed according to gender, age and disease subtypes. RESULTS: Compared with the healthy controls, abnormal rates of high density lipoprotein cholesterol (HDL-C), apolipoproteins A (ApoA) and apolipoproteins B (ApoB) in MSA patients were decreased significantly (P<0.01), while there is no difference of abnormal rates in TC, TG and LDL-C. Compared with the healthy controls, the serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), LDL-C, ApoA and ApoB levels in MSA patients were decreased significantly (P<0.01). There was no significant difference in TG levels. Compared with female MSA patients, the serum TG and LDL-C in male MSA patients were decreased significantly (P<0.05). Compared with male controls, TC, LDL-C, HDL-C, ApoA and ApoB levels of male MSA patients were decreased significantly (P<0.05) whilst there was no significant difference in TG level (P>0.05). Compared with female controls, the serum TC,TG, HDL-C, ApoA and ApoB levels in female MSA patients were decreased significantly (P<0.05) whilst there was no significant difference in LDL-C (P>0.05). There was no significant difference in lipid levels between elder patients (age over 65) and younger patients (age under 65) (P>0.05). Also no significant difference existed between type C and type P of MSA (P>0.05). No significant relationship between course of disease and lipids was found (P>0.05). CONCLUSION: Serum levels of TC, HDL-C, LDL-C, ApoA and ApoB are decreased in MSA patients but all lipid levels are not related to either disease course or subtype, which may indicate that lipids levels are related to the pathogenesis of MSA.

Chronotype and a PERIOD3 variable number tandem repeat polymorphism in Han Chinese pilots.

An association has been determined between variable number tandem-repeat (VNTR) polymorphisms in the PERIOD3 gene (PER3, rs57875989) and chronotype. An association has been found in which the longer PER3(5) allele is correlated with diurnal preference and shorter PER3(4) allele is linked with preference for evening, respectively. In this study, we explored the genotype frequency and relationship to the chronotype of a PER3 VNTR polymorphism in Han Chinese pilots compared to other populations to further develop aviation safety research. DNA samples were genotyped with respect to the 4-repeat and 5-repeat alleles of the PER3 VNTR polymorphism. We compared and analyzed PER3 VNTR genotype frequencies of a general Han Chinese population and Han Chinese pilots. The chronotypes of our subjects were evaluated by the morningness-eveningness questionnaire (MEQ). The distribution of PER3 VNTR genotype frequencies from 240 Han Chinese was determined (PER3(4/4), 78.3%; PER3(4/5), 20.0%; PER3(5/5), 1.7%) and compared to the genotype frequencies of 126 Han Chinese pilots (PER3(4/4), 71.4%; PER3(4/5), 26.1%; PER3(5/5), 2.4%). Statistical analysis revealed no significant difference between the general Han Chinese population and Han Chinese pilots regarding the PER3 VNTR genotype and allele frequencies (x(2) = 2.170, p > 0.05). Furthermore, MEQ results showed no association between the PER3 VTNR polymorphism and chronotype. However, PER3 VNTR genotype frequencies differed significantly between Han Chinese and other ethnic groups previously reported, such as Caucasians, African Americans and Italians. These data indicate that the proposed role of the PER3 VNTR needs further clarification and the role of PER3(5) allele in sleep regulation needs to be investigated in more detail. In particular, a study of PER3 polymorphisms with a larger sample size of Han Chinese individuals and Han Chinese pilots may be required.

[Comparison of tumefactive demyelinating lesions and glioma by clinical presentations and neuroimaging studies].

OBJECTIVE: To explore the clinical and imaging features of tumefactive demyelinating lesions (TDL) and glioma. METHODS: The brain computed tomography (CT), magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H-MRS) features of 60 pathologically confirmed TDL patients and 65 glioma ones, hospitalized at Navy General Hospital from 2005 to 2013, were reviewed and analyzed. RESULTS: The mean onset age of glioma was significantly older than that of TDL. The onset symptom was headache for TDL and headache and epilepsy for glioma. The features of lesions on brain CT scan: no hyperdensity in TDL group and 39 with hyperdense lesions in glioma group. Tissue necrosis was more frequently found in lesions of glioma than TDL, especially for higher grade glioma. And increased ß and γ-Glx on (1)H-MRS was most frequently found in TDL. CONCLUSION: The onset age of glioma is older than TDL. The headache is the top onset symptoms of TDL and epiplesy occurs frequently only in glioma. The hyperdense lesions on CT scan support more the diagnosis of glioma. The lesions with tissue necrosis may be a diagnostic clue for high grade glioma. On (1)H-MRS, increased ß and γ-Glx are most frequently found in TDL. Dynamic observation of imaging changes may be more important for facilitating the diagnosis of TDL, especially in conjunctions with imaging characteristics and clinical features.

[Leukoencephalopathy with cerebral calcification and cysts: a case report and review of literature].

OBJECTIVE: To improve the diagnostic ability of leukoencephalopathy with cerebral calcifications and cysts (LCC), a rare central nervous system disease. METHODS: The clinical manifestations, neuroimages and neuropathological features of a 19-year-old male patient were analyzed. A total of 20 cases from 14 literatures were reviewed. RESULT: The patient was admitted with right limb weakness, cognitive decline, headache and blurred eyesight. Head CT scan showed multiple calcifications, cysts formation and leukoencephalopathy. Brain MRI showed several cysts in bilateral hemisphere, basal ganglia, thalamus and paraventricular areas. A mural nodule was noted inside one of the cyst, which was enhanced on the contrasted MRI. The wall of the cysts was partially enhanced, but not with the fluid inside the cysts. The corresponding CT calcifications foci showed on T1 and T2 with either both hyperintensity or both hypointensity, which was also partial enhanced. Extensive leukoencephalopathy was formed around the cysts and the ventricles. But neither Cho nor NAA changed a lot on MRS. Amplitude diagram of SWI series exhibited multiple round small dark signals all over the affected areas with mixed signals showed in the phase diagram, which indicated both calcifications and microbleeding at the lesions. Neuropathological examinations found no tumor cells in the operated cyst, and showed angiomatous small blood cells were dominant in the cyst wall. Hyaline degenerations, microcalcifications and hemosiderin deposition were observed. No obvious demyelination was discovered, while gliosis, numerous Rosenthal fibers and fibrinoid vascular necrosis were found around the lesions. The clinical, neuroimaging and pathological features of this patient were in accordance with the cases reported in the literatures. CONCLUSIONS: Neuroimaging is the most important method for the diagnosis of LCC. As small vessel lesions are probably closely related to the pathophysiology of LCC, SWI could be recommended to further reveal the etiology of LCC.

[Clinical features and neuroimaging findings of 12 patients with acute disseminated encephalomyelitis involved in corpus callosum].

OBJECTIVE: To summarize the clinical features and neuroimaging findings of the patients with acute disseminated encephalomyelitis (ADEM) involved in corpus callosum (CC) so as to distinguish it from other diseases. METHODS: A total of 12 ADEM patients with the involvement of CC during the period of 2010-2012 were recruited. There were 9 males and 3 females with a mean age of 31±14 years (range: 10-54). Their clinical and neuroimaging features were retrospectively reviewed and all data analyzed by SPSS 18.0. RESULTS: (1) All of them had an acute or subacute onset. Two patients had a history of vaccination and 5 suffered upper respiratory tract infection or diarrhea. (2) The presenting symptoms included fever (n=5), headache (n=4), unsteady gait (n=2), urinary retention (n=1), indifference (n=1) and delirium (n=1). (3) The main clinical symptoms included memory loss (n=9), delirium (n=5), somnolence (n=4), urinary retention (n=9), paraplegia (n=4) and unsteady gait (n=5). (4) The examinations of cerebrospinal fluid (CSF) revealed increased intracranial pressure (n=4), leucocytosis (n=3) and increased protein (n=7) of 7 cases. All oligoclonal bands were negative. (5) The lesions were involved in bilateral CCs in 12 patients. Among them, splenium was the most commonly affected (n=9), secondly stem (n=5) and lastly genu (n=4). For 6 patients, the intracranial lesions were all in their CCs. And among them, 2 cases were involved in spinal cord. Except for CC, there were other focal lesions in brain stem and cerebellum (n=4) and spinal cord (n=6). (6) On magnetic resonance imaging (MRI), all cases showed long T2 signal intensity with blurred images. And among them, 2 cases' lesions in brain were discerned only by diffuse weighing imaging (DWI) or T2 fast fluid-attenuated inversion recovery (T2FLAIR) instead of T2-weighted. The lesions of CCs showed on gadolinium-enhanced MRI were significantly enhanced and the shapes were sheet-like (4/6). Spinal cord lesions was found in 6 cases and most spinal cord lesions were discontinuous. And the number of spinal cord segments with lesions was from 4 to 8. The shapes of lesions of spinal cord showed on enhanced MRI were like thin line. (7) Most of them were misdiagnosed as viral encephalitis (n=5), tuberculous meningoencephalitis (n=1) and brain neoplasms (n=2). And another case was admitted into urology surgery ward due to urinary retention. CONCLUSION: There are three key points about the characteristics of the ADEM patients with CC lesions: (1) They may have an adult male preponderance. The distinctive symptoms include fever, headache, delirium, somnolence, memory loss, unsteady gait and urination disorders, etc.. (2) The number of lesions on brain MRI can be multiple or single, especially the lesions of CC (mostly in splenium). On MRI, all cases showed long T2 signal intensity with blurred images so that DWI and T2 FLAIR may have a higher efficiency of detecting the lesions. In particular, multiple lesions may be all enhanced or not enhanced at equal pace on enhanced MRI. (3) In ADEM patients with CC lesions, many indices of CSF chemical examination, such as increased intracranial pressure, leucocytosis, increased protein, low sugar and low chloride, indicate the presence of intracranial infective diseases. Therefore they are most likely to be misdiagnosed as viral encephalitis or tuberculous meningoencephalitis. However, CC is not the predilection site for viral encephalitis since CC belongs to white matter but not gray matter. So ADEM should be a more appropriate diagnosis for these cases.

[The clinical features, neuroimaging findings and pathological characteristics of 26 patients with pathologically proven tumor-like inflammatory demyelinating diseases].

OBJECTIVE: To summarize the clinical features, neuroimaging findings and pathological characteristics of 26 patients with tumor-like inflammatory demyelinating diseases (TIDD) confirmed by histopathology for better diagnosis and differential diagnosis. METHODS: The clinical features, neuroimaging findings and pathological characteristics of 26 patients (14 male, 12 female) with pathologically proven TIDD (24 brain-type and 2 spinal cord-type) were retrospectively analysed. RESULTS: The mean onset age was 6 - 69 (36.7 ± 13.8) years. Twenty-one patients had good prognosis with a median followed-up duration of 51.0 months. Two patients were died of post-operative complication and pulmonary infection respectively and the remaining 3 patients were lost to followed up. The TIDD patients almost showed monophasic clinical setting. Headache, indifference accompanied with hypothesis were the commonest initial symptoms. The positive or abnormal rates of cerebrospinal fluid oligoclonal bands (OCB) and myelin basic protein (MBP) in TIDD patients were high. The involvements of bilateral and multi-lesions were commonest in TIDD (61.5%, 65.4% respectively). Twenty-two patients with CT unenhanced scanning showed hypodense lesions. Long T(1) and long T(2) signal intensity was showed on MRI and most cases appeared round-like lesion in shape. According to the shape of enhancement of the 23 patients performed with contrast agents, 11 were shown with open-ring enhancement, 4 cases (including 2 accompanied with open-ring enhancement) with complete ring enhancement, 3 with asymmetrical dotted enhancement, 2 with diffused even enhancement, and no enhancement was seen in the other 6. Furthermore, 14 cases with DWI and 12 with FLAIR all appeared hyperdensity. The typical pathological changes were demyelinating, perivascular inflammatory cells infiltration and reactive gliosis. Occasionally, the Creutzfeldt cells were also found in brain tissue of some patients. CONCLUSIONS: TIDD is a distinct demyelinating disease entity. In spite of being apt to be confused with the neoplasm in brain and spinal cord. TIDD has its own-features, for example, OCB is frequently positive in patients with TIDD and the level of MBP may be significantly increased. Furthermore, the involvements of bilateral and multi-lesions are the common in TIDD, and most cases showed open-ring enhancement or complete rim enhancement on MRI. In addition, all cases present hypodense lesions on unenhanced CT and patients with hyperdense seemed not to be considered as TIDD.

[The relationship between prion protein gene codon 129 polymorphism and Alzheimer's disease].

OBJECTIVE: To examine the relationship between prion protein gene (PRNP) codon 129 polymorphism and Alzheimer's disease (AD) by means of meta-analysis. METHODS: Odds ratios (OR) of prion protein gene codon 129 genotype distribution in AD patients against healthy control was analysed. All the relevant studies were identified and poor-qualified studies were eliminated. A meta-analysis software, Review Manager 4.2 was applied for investigating heterogeneity among individual studies and summarizing effects across studies. RESULTS: A total of 4 studies including 1095 patients and 940 controls were included but with rectification 972 cases and 658 controls of 3 studies were included. No heterogeneity among the studies was found. The pooled Peto OR (with 95% CI) of (MM + VV) vs MV is 1.10 (95% CI 0.89-1.35, P = 0.38), while the pooled Peto OR of V* vs MM is 0.80 (95% CI 0.65-0.98, P = 0.03) and the pooled Peto OR of M* vs VV is 1.38 (95% CI 1.01-1.89, P = 0.04). CONCLUSION: In European population, PRNP M and V homozygosity is not statistically significantly associated with the onset of AD. M/* genotype is associated with increased risk of AD while V/* genotype is associated with a decreased risk of AD.