Neuropsychiatric co-morbidities in non-demented Parkinson's disease

Objective:

To evaluate neuropsychiatric co-morbidities (depression, psychosis and anxiety) in non-demented patients with Parkinson''s disease (PD).

Background:

Non-motor symptoms like neuropsychiatric co-morbidities are common in Parkinson''s disease and may predate motor symptoms. Currently there is scarcity of data regarding neuropsychiatry manifestations in Indian patients with PD.

Methods:

In this cross-sectional study consecutive 126 non-demented patients with PD (MMSE ≥25) were enrolled. They were assessed using Unified Parkinson''s disease rating scale (UPDRS), Hoehn & Yahr (H&Y) stage, Schwab and England (S&E) scale of activity of daily life. Mini-international neuropsychiatric interview (MINI) was used for diagnosis of depression, psychosis and anxiety. Beck''s depression inventory (BDI), Brief psychiatric rating scale (BSRS) and Hamilton rating scale for anxiety (HAM-A) scales were used for assessment of severity of depression, psychosis and anxiety respectively.

Results:

Mean age and duration of disease was 57.9 ± 10.9 years and 7.3 ± 3.6 years respectively. At least one of the neuropsychiatric co-morbidity was present in 64% patients. Depression, suicidal risk, psychosis and anxiety were present in 43.7%, 31%, 23.8% and 35.7% respectively. Visual hallucinations (20.6%) were most frequent, followed by tactile (13.5%), auditory (7.2%) and olfactory hallucinations (1.6%). Patients with depression had higher motor disability (UPDRS-motor score 33.1 ± 14.0 vs 27.3 ± 13.3; and UPDRS-total 50.7 ± 21.8 vs 41.0 ± 20.3, all p values <0.05). Patients with psychosis were older (63.6 ± 8.0 years vs 56.1 ± 11.1 years, p < 0.05) and had longer duration of illness (8.6 ± 3.4 years vs 6.9 ± 3.5, p < 0.05).

Conclusions:

About two third patients with Parkinson''s disease have associated neuropsychiatric co-morbidities. Depression was more frequent in patients with higher disability and psychosis with longer duration of disease and older age. These co-morbidities need to be addressed during management of patients with PD.     

Intergenotypic variation of Vitamin B12 and Folate in AD: In north indian population

Objectives:

Changes in lifestyle habits such as diet modification or supplementation have been indicated as probable protective factors for a number of chronic conditions including Alzheimer''s disease (AD). With this background, we aim to hypothesize that whether C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene contributes towards the risk of developing AD and its association with vitamin B12 and folate levels.

Materials and Methods:

A case-control study comprising of total 200 subjects, within the age group of 50-85 years. Their blood samples were analyzed for serum folate, vitamin B12 levels, and MTHFR C677T polymorphism by restriction fragment length polymorphism (RFLP).

Results:

The mean plasma levels of vitamin B12 and folate were significantly lower in study group when compared to the control group (P < 0.001). Genotypic and allelic frequency of MTHFR gene in both groups was found to be significant (P < 0.05). The intergenotypic variations of vitamin B12 and folate were found to be significant (P < 0.001).

Conclusion:

We concluded that the subjects with homozygous mutated alleles are more prone to AD and also pointed out the influence of presence/absence of MTHFR T allelic variants on serum folate and vitamin B12 levels.     

Automated Classification to Predict the Progression of Alzheimer's Disease Using Whole-Brain Volumetry and DTI

Objective

This study proposes an automated diagnostic method to classify patients with Alzheimer''s disease (AD) of degenerative etiology using magnetic resonance imaging (MRI) markers.

Methods

Twenty-seven patients with subjective memory impairment (SMI), 18 patients with mild cognitive impairment (MCI), and 27 patients with AD participated. MRI protocols included three dimensional brain structural imaging and diffusion tensor imaging to assess the cortical thickness, subcortical volume and white matter integrity. Recursive feature elimination based on support vector machine (SVM) was conducted to determine the most relevant features for classifying abnormal regions and imaging parameters, and then a factor analysis for the top-ranked factors was performed. Subjects were classified using nonlinear SVM.

Results

Medial temporal regions in AD patients were dominantly detected with cortical thinning and volume atrophy compared with SMI and MCI patients. Damage to white matter integrity was also accredited with decreased fractional anisotropy and increased mean diffusivity (MD) across the three groups. The microscopic damage in the subcortical gray matter was reflected in increased MD. Classification accuracy between pairs of groups (SMI vs. MCI, MCI vs. AD, SMI vs. AD) and among all three groups were 84.4% (±13.8), 86.9% (±10.5), 96.3% (±4.6), and 70.5% (±11.5), respectively.

Conclusion

This proposed method may be a potential tool to diagnose AD pathology with the current clinical criteria.     

The Effects of Galantamine Treatment on Attention and Its Relationship with Cognition and Activities of Daily Living in Patients with Mild to Moderate Alzheimer's Disease

Background and Purpose

The positive effects of galantamine on cognition and activities of daily living (ADL) in Alzheimer''s disease (AD) are thought to be mediated via improvements in attention. The purpose of this study was to determine the effect of galantamine on attention in AD patients using a computerized attention test and to elucidate the relationship between improvements in attention and change in cognition and ADL.

Methods

In this multicenter, open-label, prospective study, patients with mild to moderate AD received galantamine and then submitted to computerized attention tests, the Alzheimer''s Disease Assessment Scale-cognitive subscale, and instrumental ADL (IADL) at baseline, 4 weeks, and 12 weeks. The differences in reaction time on computerized tests were explored relative to the changes in cognition and IADL.

Results

After 12 weeks of taking the trial medication there was a significant reduction from baseline levels in the choice reaction time (baseline, 5,216±3,650 sec; 12 weeks, 4,139±2,920 sec; p<0.01) and the simple reaction time (baseline, 1,089±782 sec; 12 weeks, 908±606 sec; p<0.01). Correlation analyses of changes in choice or simple reaction times relative to cognition and ADL measures yielded no significant associations. The improvement in attention observed at 4 weeks of galantamine treatment was not associated with any significant changes in outcome measures at the end of trial.

Conclusions

This study found no significant association between the improvement in attention after treatment with galantamine and changes in cognition and ADL in patients with mild to moderate AD, despite the significant improvement in attention over the course of the treatment.     

Longitudinal SPECT study in Alzheimer's disease: relation to apolipoprotein E polymorphism

OBJECTIVES—In mild Alzheimer'sdisease, SPECT imaging of regional cerebral blood flow has highlighteddeficits in the posterior association cortex, and later in the diseaseprocess, the deficit spreads to involve the frontal cortex. The ε4allele of apolipoprotein E is a risk factor for Alzheimer's disease.The effect of apolipoprotein E polymorphism on cerebral perfusion wasstudied. The hypothesis was that those patients with Alzheimer'sdisease who carry the ε4 allele would have more severe cerebral hypoperfusion.
METHODS—Thirty one patients with Alzheimer'sdisease and eight age and sex matched control subjects were examined ina three year longitudinal study. Patients with Alzheimer's diseasewere divided into subgroups according to their number of ε4 alleles.Regional cerebral blood flow ratios referred to the cerebellum wereexamined by ^99mTc-HMPAO SPECT. Apolipoprotein E genotypeswere determined by digestion of polymerase chain reaction products withthe restriction enzyme Hha1.
RESULTS—All patients with Alzheimer's disease hadbilateral temporoparietal hypoperfusion compared with control subjects.The two ε4 allele subgroups had the lowest ratios at the baselineassessment in the parietal and occipital cortices, and at the follow upin the temporal, parietal, and occipital cortices. They had the highest reduction in percentage terms in the temporal and occipital cortices compared with the other subgroups. However, the global clinical severity did not differ at the baseline or follow up examinations between the subgroups.
CONCLUSION—Apolipoprotein E polymorphism isinvolved in the pathogenesis and heterogeneity of Alzheimer's diseaseas the most severe cerebral hypoperfusion was found in the ε4 allelesubgroups. This might have implications for therapeutic approaches inAlzheimer's disease.

     

A cross-sectional study on thyroid status in North Indian elderly outpatients with dementia

Background:

Several population based studies have demonstrated an association between hypo-or hyperthyroidism and dementia in last two decades. As a consequence, thyroid stimulating hormone has become part of the screening laboratory test for dementia.

Aim:

The aim of the present study was to evaluate the association between thyroid function and Alzheimer''s disease (AD) and vascular dementia (VaD) and to determine the risk of AD and VaD in clinically euthyroid patients.

Materials and Methods:

A cross-sectional hospital based study was carried out in subjects diagnosed with AD/VaD and were assessed for thyroid status as routine screening test.

Results:

Free T3, free T4 and TSH were studied in 114 AD patients (mean age: 65 years), 35 VaD patients (mean age: 62 years) and 105 control subjects (mean age: 62 years). In AD group, TSH levels were significantly lower than controls (P = 0.00) and for each unit increase in TSH level, the odds of having dementia decreased by 37.1%. No such relation was seen in VaD.

Conclusion:

The results suggest a consistent association of subclinical hyperthyroidism and AD.     

Alterations in Polysomnographic (PSG) profile in drug-na?ve Parkinson's disease

Objective:

We studied the changes in Polysomnographic (PSG) profile in drug-naïve patients of Parkinson''s disease (PD) who underwent evaluation with sleep overnight PSG.

Materials and Methods:

This prospective study included 30 with newly diagnosed levodopa-naïve patients with PD, fulfilling the UK-PD society brain bank clinical diagnostic criteria (M:F = 25:5; age: 57.2 ± 10.7 years). The disease severity scales and sleep related questionnaires were administered, and then patients were subjected to overnight PSG.

Results:

The mean duration of illness was 9.7 ± 9.5 months. The mean Hoehn and Yahr stage was 1.8 ± 0.4. The mean Unified Parkinson''s Disease Rating Scale (UPDRS) motor score improved from 27.7 ± 9.2 to 17.5 ± 8.9 with sustained usage of levodopa. Nocturnal sleep as assessed by Pittsburgh Sleep Quality Index (PSQI) was impaired in 10 (33.3%) patients (mean PSQI score: 5.1 ± 3.1). Excessive day time somnolence was recorded in three patients with Epworth Sleepiness Scale (ESS) score ≥ 10 (mean ESS score: 4.0 ± 3.4). PSG analysis revealed that poor sleep efficiency of <85% was present in 86.7% of patients (mean: 68.3 ± 21.3%). The latencies to sleep onset (mean: 49.8 ± 67.0 minutes) and stage 2 sleep (36.5 ± 13.1%) were prolonged while slow wave sleep was shortened. Respiration during sleep was significantly impaired in which 43.3% had impaired apnoea hyperpnoea index (AHI) ≥5, mean AHI: 8.3 ± 12.1). Apnoeic episodes were predominantly obstructive (obstructive sleep apnea, OSA index = 2.2 ± 5.1). These patients had periodic leg movement (PLM) disorder (56.7% had PLM index of 5 or more, mean PLMI: 27.53 ± 4 9.05) that resulted in excessive daytime somnolence.

Conclusions:

To conclude, sleep macro-architecture is altered in frequently and variably in levodopa-naïve patients of PD and the alterations are possibly due to disease process per se.     

Association between apolipoprotein E gene polymorphism and Alzheimer's disease in Uighur and Han populations

Aim: Currently, there are almost 100 genes related to Alzheimer's disease (AD), and studies have indicated that apolipoprotein E (APO E) ε4 allele is a genetic risk factor of AD. However, there have been no reports of the distributions of APO E genotypes and allele frequencies in Uighur and Han AD patients. Methods: We analyzed APO E gene polymorphism in 209 AD cases diagnosed based on National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association and 220 non‐dementia controls. We used polymerase chain reaction‐restriction fragment length polymorphism methods as the basis of this epidemiological survey. Results: In the AD and control groups, there are no statistically significant differences in APO E genotypes and allele frequency between the Uighur and Han ethnicities (P < 0.05). In the AD group, the ε3/4 genotype (28.2%) and ε4 allele frequency (14.8%) occurred at a higher rate than in the control (13.2% and 8.0%, respectively; P < 0.05). This distinction remained true within each ethnicity; the ε3/4 genotype and ε4 allele frequency are higher in the AD groups (Uighur, 30.6% and 15.8%, respectively; Han, 25.5% and 13.8%, respectively) than in the control groups (Uighur, 14.5% and 9.4%, respectively; Han, 11.7% and 6.3%, respectively; P < 0.05). Conclusions: The distribution of APO E genotype and allele frequency does not differ between the Uighur and Han ethnicities. The APO E ε4 allele is a risk factor of AD for both populations.     

Quantitative EEG and medial temporal lobe atrophy in Alzheimer's dementia: Preliminary study

Backgrounds:

The electroencephalogram (EEG) abnormalities in Alzheimer''s disease (AD) have been widely reported, and medial temporal lobe atrophy (MTLA) is one of the hallmarks in early stage of AD. We aimed to assess the relationship between EEG abnormalities and MTLA and its clinical validity.

Materials and Methods:

A total of 18 patients with AD were recruited (the mean age: 77.83 years). Baseline EEGs were analyzed with quantitative spectral analysis. MTLA was assessed by a T1-axial visual rating scale (VRS).

Results:

In relative power spectrum analysis according to the right MTLA severity, the power of theta waves in C4, T4, F4, F8, and T5 increased significantly and the power of beta waves in T6, C4, T4, F8, T5, P3, T3, and F7 decreased significantly in severe atrophy group. In relative power spectrum analysis according to the left MTLA severity, the power of theta waves in T3 increased significantly and that of beta waves in P4, T6, C4, F4, F8, T5, P3, C3, T3, F3, and F7 decreased significantly in severe atrophy group.

Conclusion:

The severe MTLA group, regardless of laterality, showed more severe quantitative EEG alterations. These results suggest that quantitative EEG abnormalities are correlated with the MTLA, which may play an important role in AD process.     

Effects of Apolipoprotein E Genotype on Cortical Neuropathology in Senile Dementia of the Lewy Body and Alzheimer's Disease

Apolipoprotein E (APO E) genotypes were determined in a UK population of neuropathologically confirmed control cases, and in cases of Lewy body dementia (SDLT) and late onset Alzheimer's disease (AD). APO E ϵ4 allele frequency was significantly elevated in both SDLT and AD groups with a concomitant reduction in the APO E ϵ3 allele frequency. The ϵ2 allele frequency in the AD group was only 25% of the control population, though because of the relatively small sample size this reduction was not significant; the ϵ2 allele frequency in the SDLT group was normal. No significant association was found between senile plaque density and neurofibrillary tangle density in the neocortex and APO E allele dose in either SDLT or AD. Although the possession of APO E ϵ4 is associated with an increased risk of developing SDLT and AD, actual APO E genotype does not appear to affect the burden of pathology.     

Apolipoprotein E genotypes and longevity across dementia disorders

Introduction

The ε4 allele of the apolipoprotein E (APOE) gene is a prominent risk factor for Alzheimer's disease (AD), but its implication in other dementias is less well studied.

Serial macro-architectural alterations with levodopa in Parkinson's disease: Polysomnography (PSG)-based analysis

Purpose:

We studied the sleep macroarchitecture with polysomnography (PSG) in drug naïve patients with Parkinson''s disease (PD) and reassessed them following treatment with levodopa.

Materials and Methods:

This prospective hospital-based study included 15 patients with PD (age: 59 ± 11.2 years, duration of PD: 11.8 ± 12.3 months; and male: female (M:F) = 11:4). They were assessed for demography, phenotype, modified Hoehn and Yahr staging (H & Y); Schwab and England and Activities of Daily Living (S and E ADL) Scale; and Unified PDRating Scale (UPDRS). Sleep was assessed using Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and National Institute of Mental Health and Neurosciences (NIMHANS) comprehensive sleep disorder questionnaire. They underwent overnight PSG at baseline and after13.3 ± 5.7 months of levodopa (440 mg/day).

Results:

Patients with PD had responded to levodopa as indicated by the significant improvement in UPDRS motor score in ON state compared to OFF state. Nocturnal sleep quality indices did not vary significantly, but the excessive daytime somnolence improved (P = 0.04) with levodopa. Sleep efficiency (P = 0.65), latency to sleep onset (P = 0.19), latency to stage 1 (P = 0.12), and duration of stage 1 (P = 0.55) had increased. Duration of ‘awake in bed’ (P = 0.24), slow wave sleep (P = 0.29), and rapid eye movement (REM) sleep (P = 0.24) decreased with treatment. Periodic leg movements (PLMs) had reduced (P = 0.68) and mean oxygen saturation during sleep improved (P = 0.002). Surprisingly, snore index (P < 0.03) during sleep had increased with levodopa.

Conclusions:

Sleep alterations in PD occur even in early stages due to the disease process. There was improvement in most of the parameters of sleep macroarchitecture with levodopa.     

The APOE ?4/?4 genotype potentiates vascular fibrin(ogen) deposition in amyloid-laden vessels in the brains of Alzheimer's disease patients

Evidence indicates a critical role for cerebrovascular dysfunction in Alzheimer''s disease (AD) pathophysiology. We have shown that fibrin(ogen), the principal blood-clotting protein, is deposited in the AD neurovasculature and interacts with beta-amyloid (Aβ), resulting in increased formation of blood clots. As apolipoprotein E (ApoE), a lipid-transporting protein with three human isoforms (E2, E3, and E4), also binds to Aβ, we hypothesized that ApoE and fibrin(ogen) may have a combined effect on the vascular pathophysiology in AD. We assessed whether APOE genotype differentially influences vascular fibrin(ogen) deposition in postmortem brain tissue using immunohistochemistry. An increased deposition of fibrin(ogen) was observed in AD cases compared with non-demented controls, and there was a strong correlation between cerebral amyloid angiopathy (CAA) severity and fibrin(ogen) deposition. Moreover, brains from AD cases homozygous for APOE ɛ4 showed increased deposition of fibrin(ogen), specifically in CAA- and oligomeric Aβ-positive vessels compared with AD APOE ɛ2 and ɛ3 allele carriers, an effect that was not directly linked to CAA severity and cerebrovascular atherosclerosis. These data further support a role for fibrin(ogen) in AD pathophysiology and link the APOE ɛ4/ɛ4 genotype with increased thrombosis and/or impaired fibrinolysis in the human AD brain.     

Incidence and Cognitive Decline of Alzheimer’s Disease and Other Dementia by Apolipoprotein ε4 Allele Presence: A Community-Based Cohort Study in Korean Elderly

Objective This study aimed to investigate the role of apolipoprotein E (APOE) ε4 allele to the incidence of dementia and cognitive decline in a cohort of a Korean community. Methods From a community-based dementia-free cohort, 357 participants were genotyped. Participants underwent 2 cognitive assessments separated by a hiatus between 6 to 7 years and were diagnosed as healthy control (n=297), Alzheimer’s disease (AD) (n=44), and other dementia (n=16) at the second assessment. Incidence risk and onset age of disease according to APOE ε4 presence were analyzed in AD and other dementia. Differences in cognitive decline rate depending on APOE ε4 were also examined across all groups. Results The relative risks and onset age of dementia were not different by the presence of the APOE ε4 allele. Cognitive decline was more prominent in the presence of APOE ε4 allele (score change=7.4) than non-presence (score change=3.1), and this interaction was significant only in the AD group (F=10.51, p=0.003). Conclusion The APOE ε4 alleles can be a critical factor in predicting cognitive change for AD in the Korean community population but not in predicting AD incidence. This finding suggest that clinicians consider the presence of APOE ε4 allele examining patients with rapid declining dementia.     

Apolipoprotein E4 Genotype and Depressive Symptoms as Risk Factors for Dementia in an Older Korean Population

Objective

Growing evidence suggests the separate associations of apolipoprotein E e4 allele (apo E4) and depression with incident dementia. This study investigated the separate and combined effects of apo E4 and depression on the incidence of dementia in both men and women.

Methods

Of 625 elderly without dementia at baseline, 518 (83%) were followed over a 2.4-year period and were assessed clinically for incident dementia. The apo E polymorphism was ascertained, and depression was identified using the Korean version of the Geriatric Depression Scale (KGDS). Covariates included age, gender, education, disability, alcohol history, physical activity, and vascular risk factors.

Results

The incidence of dementia was significantly higher in elderly Koreans with both apo E4 and depression compared to those without both factors [adjusted odds ratio (95% CI)=5.85 (1.77-19.38)]. This interaction was significant in men (p=0.049), but not in women (p=0.354).

Conclusion

Depressed elderly people are at great risk for incident dementia in the presence of apo E4. Potential gender differences require further evaluation.     

Sleep disturbances in drug na?ve Parkinson's disease (PD) patients and effect of levodopa on sleep

Context:

Parkinson''s disease (PD) is associated with sleep disturbances, attributed to the neurodegenerative process and therapeutic drugs. Studies have found levodopa to increase wakefulness in some patients while increasing sleepiness in others.

Aims:

To confirm sleep disturbances in drug naïve PD patients and understand the impact of levodopa on their sleep.

Materials and Methods:

Twenty-three drug naïve PD patients and 31 age-gender matched controls were compared using the Parkinson''s Disease Sleep Scale (PDSS) and Epworth Sleepiness Scale (ESS). A polysomnogram objectively compared sleep quality. Of the 23 patients, the 12 initiated on levodopa were reassessed subjectively and through polysomnography after 2 months of therapy.

Statistical Analysis:

Data was expressed as mean ± standard deviation, median, and range. Continuous variables were analyzed by Student''s T test for normally distributed data and Mann–Whitney U test for skewed data. Discrete variables were compared by Chi Square tests (Pearson Chi square Test or Fisher''s Exact Test). Wilcoxon signed ranks test was applied in the analysis of paired data pre- and post-levodopa. A P value < 0.05 was considered as statistically significant. Statistical analysis of the data was done using the Statistical Package for the Social Sciences (SPSS) version 12.

Results:

Drug naïve PD patients had lower PDSS scores than controls. The sleep architecture changes observed on polysomnogram were reduced NREM Stage III and REM sleep and increased sleep latency and wake after sleep onset time. Following levodopa, improved sleep efficiency with reduced sleep latency and wake after sleep onset time was noted, coupled with improved PDSS scores. However, NREM Stage III and REM sleep duration did not increase.

Discussion:

PD patients take longer to fall asleep and have difficulty in sleep maintenance. Sleep maintenance is affected by nocturia, REM behavioral disorder, nocturnal cramps, akinesia, and tremors, as observed in PDSS scores. Levodopa improves sleep efficiency by improving motor scores without altering sleep architecture.

Conclusions:

Poor sleep quality and sleep architecture changes occur secondary to the neurodegenerative process in PD patients. Though levodopa improves sleep quality by reducing rigidity and tremor, it does not reverse sleep architecture changes.     

Amyloid-β depresses excitatory cholinergic synaptic transmission in Drosophila

Objective Decline, disruption, or alterations of nicotinic cholinergic mechanisms contribute to cognitive dysfunctions like Alzheimer’s disease (AD). Although amyloid-β (Aβ) aggregation is a pathological hallmark of AD, the mechanisms by which Aβ peptides modulate cholinergic synaptic transmission and memory loss remain obscure. This study was aimed to investigate the potential synaptic modulation by Aβ of the cholinergic synapses between olfactory receptor neurons and projection neurons (PNs) in the olfactory lobe of the fruit fly. Methods Cholinergic spontaneous and miniature excitatory postsynaptic current (mEPSC) were recorded with whole-cell patch clamp from PNs in Drosophila AD models expressing Aβ40, Aβ42, or Aβ42Arc peptides in neural tissue. Results In fly pupae (2 days before eclosion), overexpression of Aβ42 or Aβ42Arc, but not Aβ40, led to a significant decrease of mEPSC frequency, while overexpression of Aβ40, Aβ42, or Aβ42Arc had no significant effect on mEPSC amplitude. In contrast, Pavlovian olfactory associative learning and lifespan assays showed that both short-term memory and lifespan were decreased in the Drosophila models expressing Aβ40, Aβ42, or Aβ42Arc. Conclusion Both electrophysiological and behavioral results showed an effect of Aβ peptide on cholinergic synaptic transmission and suggest a possible mechanism by which Aβ peptides cause cholinergic neuron degeneration and the consequent memory loss.     

The neuroprotective effect of immune serum of adeno-associated virus vaccine containing Aβ1-15 gene on amyloid toxicity

Objective:

The aim of this study was to explore the effect of adeno-associated virus (AAV) serotype 2 vector vaccine containing amyloid-β peptide (Aβ) 1-15 gene fragment (AAV-Aβ15) immunized mice sera on counteracting Aβ1-42 peptide toxicity towards a primary culture cortical neurons.

Materials and Methods:

BALB/c mice were vaccinated via the intramuscular immunization route with AAV-Aβ15. The anti-Aβ antibody titer of immunized mice sera was quantified by sandwich Enzyme-Linked ImmunoSorbent Assay. The toxicity of Aβ1-42 peptide on neurons was assessed by morphology with an inverse microscopy and cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.

Results:

AAV-Aβ15 could induce an Aβ-specific immunoglobulin G (IgG) humoral immune response in /c mice the anti-Aβ antibodies were detectable at 1 month after immunization, significantly increased at 2 and 4 months after immunization, and the immunized sera could attenuate cytotoxicity of Aβ1-42 peptide on primary culture cortical neurons.

Conclusions:

The immune serum of AAV-Aβ15 could play a neuroprotective effect against Aβ1-42 peptide toxicity, which would be beneficial for Alzheimer''s disease patients.Key Words: Alzheimer''s disease, amyloid-beta, immunotherapy, vaccine