Incidence and viral aetiologies of acute respiratory illnesses (ARIs) in the United States: a population-based study.

We conducted prospective, community-wide surveillance for acute respiratory illnesses (ARIs) in Rochester, NY and Marshfield, WI during a 3-month period in winter 2011. We estimated the incidence of ARIs in each community, tested for viruses, and determined the proportion of ARIs associated with healthcare visits. We used a rolling cross-sectional design to sample participants, conducted telephone interviews to assess ARI symptoms (defined as a current illness with feverishness or cough within the past 7 days), collected nasal/throat swabs to identify viruses, and extracted healthcare utilization from outpatient/inpatient records. Of 6492 individuals, 321 reported an ARI within 7 days (4·9% total, 5·7% in Rochester, 4·4% in Marshfield); swabs were collected from 208 subjects. The cumulative ARI incidence for the entire 3-month period was 52% in Rochester [95% confidence interval (CI) 42-63] and 35% in Marshfield (95% CI 28-42). A specific virus was identified in 39% of specimens: human coronavirus (13% of samples), rhinovirus (12%), RSV (7%), influenza virus (4%), human metapneumovirus (4%), and adenovirus (1%). Only 39/200 (20%) had a healthcare visit (2/9 individuals with influenza). ARI incidence was ~5% per week during winter.

Integrating ecology with management to control wildlife brucellosis.

Bison (Bison bison) and elk (Cervus elaphus) in the greater Yellowstone ecosystem have long been infected with Brucella abortus. The continued culling of large numbers of Yellowstone bison to reduce the risk of brucellosis transmission to cattle could negatively affect long-term conservation. A desirable management objective is to reduce the level of B. abortus infection while conserving wildlife populations. Identifying the ecological factors that influence immune suppression and vulnerabilityto infection will help initiate effective control measures. Seasonal food restriction during pregnancy has the potential to limit resources available for immune defence and may be an important factor sustaining brucellosis in wild ungulate populations. Consequently, effective management practices will need to include a diverse range of integrated methods, which include maintaining separation of livestock and wildlife, managing habitat to reduce brucellosis transmission, and reducing disease prevalence in wildlife. The long-term success of these management practices will depend on sound science and support of the stakeholders involved.

Bovine brucellosis in wildlife: using adaptive management to improve understanding, technology and suppression.

Eradication of brucellosis from bison (Bison bison) and elk (Cervus elaphus) populations in the Greater Yellowstone Area is not possible with current technology. There are considerable uncertainties regarding the effectiveness of management techniques and unintended effects on wildlife behaviour and demography. However, adaptive management provides a framework for learning about the disease, improving suppression techniques, and lowering brucellosis transmission among wildlife and to cattle. Since it takes approximately three years after birth for female bison to become reproductively active and contribute to brucellosis transmission, there is an opportunity to implement actions such as vaccination and the selective removal of infectious bison based on age and assay results to reduce the potential for transmission. Older adult bison that have been exposed to the bacteria, but recovered from acute infection, could be retained in the population to provide some immunity (resistance) against future transmission. Through careful predictions, research, and monitoring, our understanding and technology will be improved and management actions can be adjusted to better achieve desired outcomes.

Promoting nurse-led behaviour change interventions to prevent cardiovascular disease in disadvantaged communities: A scoping review.

Cardiovascular diseases (CVD) are the leading cause of death worldwide and they disproportionally affect people living in disadvantaged communities. Nurse-led behaviour change interventions have shown great promise in preventing CVD. However, knowledge regarding the impact and nature of such interventions in disadvantaged communities is limited. This review aimed to address this knowledge gap. A six-stage scoping review framework developed by Arksey and O'Malley, with revisions by Levac et al., was used. The search process was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Extension for Scoping Reviews (PRISMA-ScR). Three electronic databases were searched (PUBMED/MEDLINE, CINAHL Plus, and Cochrane CENTRAL), and included studies were analysed using Braun and Clarke's 'Thematic Analysis' approach. Initial searches yielded 952 papers and 30 studies were included in the review following duplicate, title/abstract, and full-text screening. The included studies indicate that nurse-led behaviour change primary prevention interventions in disadvantaged areas are largely effective; albeit the considerable variety of intervention approaches, study populations and outcome measures used to date make it difficult to ascertain this. Other identified key areas in the promotion of nurse-led behaviour change included tailoring interventions to specific populations, providing adequate training for nurses, overcoming patient access difficulties and encouraging patient engagement. Overall, the findings indicate that nurse-led behaviour change interventions for high-risk CVD patients in disadvantaged areas show much promise, although there is considerable variety in the interventions employed and studied to date. Further research is needed to examine the unique barriers and facilitators of interventions for specific disadvantaged groups.

TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation.

We and others recently reported tumor necrosis factor (TNF) and apoptosis ligand-related leukocyte-expressed ligand 1 (TALL-1) as a novel member of the TNF ligand family that is functionally involved in B cell proliferation. Transgenic mice overexpressing TALL-1 have severe B cell hyperplasia and lupus-like autoimmune disease. Here, we describe expression cloning of a cell surface receptor for TALL-1 from a human Burkitt's lymphoma RAJI cell library. The cloned receptor is identical to the previously reported TNF receptor (TNFR) homologue transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). Murine TACI was subsequently isolated from the mouse B lymphoma A20 cells. Human and murine TACI share 54% identity overall. Human TACI exhibits high binding affinities to both human and murine TALL-1. Soluble TACI extracellular domain protein specifically blocks TALL-1-mediated B cell proliferation without affecting CD40- or lipopolysaccharide-mediated B cell proliferation in vitro. In addition, when injected into mice, soluble TACI inhibits antibody production to both T cell-dependent and -independent antigens. By yeast two-hybrid screening of a B cell library with TACI intracellular domain, we identified that, like many other TNFR family members, TACI intracellular domain interacts with TNFR-associated factor (TRAF)2, 5, and 6. Correspondingly, TACI activation in a B cell line results in nuclear factor kappaB and c-Jun NH(2)-terminal kinase activation. The identification and characterization of the receptor for TALL-1 provides useful information for the development of a treatment for B cell-mediated autoimmune diseases such as systemic lupus erythematosus.

Recombinant HA-based vaccine outperforms split and subunit vaccines in elicitation of influenza-specific CD4 T cells and CD4 T cell-dependent antibody responses in humans.

Although traditional egg-based inactivated influenza vaccines can protect against infection, there have been significant efforts to develop improved formats to overcome disadvantages of this platform. Here, we have assessed human CD4 T cell responses to a traditional egg-based influenza vaccine with recently available cell-derived vaccines and recombinant baculovirus-derived vaccines. Adults were administered either egg-derived Fluzone®, mammalian cell-derived Flucelvax® or recombinant HA (Flublok®). CD4 T cell responses to each HA protein were assessed by cytokine EliSpot and intracellular staining assays. The specificity and magnitude of antibody responses were quantified by ELISA and HAI assays. By all criteria, Flublok vaccine exhibited superior performance in eliciting both CD4 T cell responses and HA-specific antibody responses, whether measured by mean response magnitude or percent of responders. Although the mechanism(s) underlying this advantage is not yet clear, it is likely that both qualitative and quantitative features of the vaccines impact the response.

Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE.

Cerebral deposition of amyloid beta peptide (Abeta) is an early and critical feature of Alzheimer's disease. Abeta generation depends on proteolytic cleavage of the amyloid precursor protein (APP) by two unknown proteases: beta-secretase and gamma-secretase. These proteases are prime therapeutic targets. A transmembrane aspartic protease with all the known characteristics of beta-secretase was cloned and characterized. Overexpression of this protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were cleaved exactly and only at known beta-secretase positions. Antisense inhibition of endogenous BACE messenger RNA decreased the amount of beta-secretase cleavage products, and purified BACE protein cleaved APP-derived substrates with the same sequence specificity as beta-secretase. Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for beta-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease.

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 18-49 years of age, naive to 23-valent pneumococcal polysaccharide vaccine.

BACKGROUND: Based on the success of vaccination with pneumococcal conjugate vaccines (PCVs) in children, recent studies have focused on PCVs in adults. Data from a randomized, double-blind study comparing the immunogenicity, tolerability, and safety of the 13-valent PCV (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in PPSV23-naive adults 60-64 years of age have been published. The same study also included a cohort of adults aged 18-49 years that received open-label PCV13. The purpose of this cohort was to examine the immunogenicity, safety, and tolerability of PCV13 in adult subjects 18-49 years of age compared with adults 60-64 years of age for whom PCV13 is approved. METHODS: Adults naive to PPSV23 were grouped by age into 2 cohorts: 18-49 years (n=899; further stratified by age into 3 subgroups 18-29, 30-39, and 40-49 years) and 60-64 years (n=417). All subjects received 1 dose of PCV13. In both age groups, immunogenicity was assessed by antipneumococcal opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) 1 month after vaccination. Safety and tolerability were evaluated. RESULTS: In adults aged 18-49 years, OPA GMTs and IgG GMCs were noninferior for all 13 serotypes and statistically significantly higher for all except 1 serotype (OPA GMT) and 5 serotypes (IgG GMCs) compared with adults 60-64 years. Immune responses were highest in the youngest age subgroup (18-29 years). Local reactions and systemic events were more common in adults 18-49 years compared with 60-64 years and were self-limited. CONCLUSION: Immune responses to PCV13 are robust in adults ≥18 years of age, with highest responses observed in the youngest subgroup. Based on its safety and immunologic profile, PCV13 may serve an important therapeutic role in younger adults, particularly those with underlying medical conditions who have an increased risk of serious pneumococcal infections.

Production of influenza-stimulated tumor necrosis factor-alpha by monocytes following acute influenza infection in humans.

Tumor necrosis factor-alpha (TNF-alpha) is often measured in the serum or plasma of patients with severe infections, and marked elevation correlates with poor outcome. The relationship of TNF-alpha to protection from disease is frequently not observed because prospective studies of infectious agents are difficult to perform. We took advantage of a human antiviral influenza challenge study to correlate TNF-alpha production with seroconversion and symptom development. TNF-alpha production was measured by ELISA in the plasma compartment or was measured by intracellular production at the single cell level in the monocyte gated population. Monocyte TNF-alpha was associated with asymptomatic seroconversion, whereas there was no change in the plasma at the times measured. Measurement of TNF-alpha at the single cell level by flow cytometry may allow for better differentiation of the protective role of this cytokine in future studies.

Nucleotide sequence of the avian influenza A/Mallard/NY/6750/78 virus polymerase genes.

The avian influenza A/Mallard/NY/6750/78 virus is currently being evaluated as a donor of attenuating genes in the construction of live avian-human influenza A reassortant virus vaccines for use in humans. We determined the nucleotide sequences of the three polymerase gene segments of this virus. This completes the nucleotide sequence of the six transferrable genes of the avian donor virus. Comparison of the nucleotide and deduced amino acid sequences of the non-glycoprotein genes of the avian A/Mallard/78 virus with representative avian and human influenza A viruses suggests that the PB1 gene of H2N2 subtype human influenza A viruses may have been derived from a non-human, possibly avian influenza A virus by genetic reassortment. In addition, several regions of conserved amino acids with potential functional significance were identified in the deduced amino acid sequences of the polymerase proteins.

The attenuation phenotype conferred by the M gene of the influenza A/Ann Arbor/6/60 cold-adapted virus (H2N2) on the A/Korea/82 (H3N2) reassortant virus results from a gene constellation effect.

A single gene reassortant (SGR) virus that derived its M gene from the attenuated influenza A/Ann Arbor/6/60 cold-adapted (CA) donor virus and the remaining genes from the A/Korea/82 (H3N2) wild type (WT) virus (designated A/Korea/82 CA M-SGR) was previously shown to be attenuated in mice, hamsters, ferrets, and humans. The attenuation (ATT) phenotype of this SGR virus could result directly from an altered function of the mutant M gene product of the A/Ann Arbor/6/60 CA virus, which differs from the M gene of the A/Ann Arbor/6/60 WT virus at only one amino acid or, indirectly from a gene constellation effect in which ATT results from an inefficient interaction between the products of the M gene of the A/Ann Arbor/6/60 virus and other genes of the A/Korea/82 virus. Several lines of evidence from the present study are consistent with our interpretation that the ATT phenotype of the A/Korea/82 CA M-SGR results from a gene constellation effect. First, the A/Korea/82 CA M-SGR and an A/Korea/82 SGR containing the A/Ann Arbor/6/60 WT M gene were each restricted in replication in the upper and lower respiratory tract of mice compared with the A/Korea/82 WT virus. Second, an A/Udorn/72 CA M-SGR containing the M gene from the A/Ann Arbor/6/60 CA donor virus in a background of other genes derived from the A/Udorn/72 (H3N2) WT virus was not attenuated in the respiratory tract of mice. These data suggest that the change in the amino acid sequence of the M gene product from the A/Ann Arbor/6/60 WT to CA virus is not responsible for the ATT phenotype of the A/Korea/82 CA M-SGR. In addition, evidence of the genetic instability of the A/Korea/82 CA M-SGR is presented, specifically, an extragenic mutation that results in loss of the ATT phenotype. The implications of these findings for the ATT phenotype of the live attenuated reassortant viruses derived from the A/Ann Arbor/6/60 CA donor virus are discussed.

Evaluation of the protective efficacy of a serotype 1 bovine-human rotavirus reassortant vaccine in infants.

The objective of this study was to evaluate the efficacy of a live, attenuated bovine (strain WC3) x human (strain WI79, serotype G1) rotavirus reassortant (WI79-9) virus vaccine for prevention of symptomatic rotavirus gastroenteritis in infants. The study was a prospective, randomized, double-blind, placebo-controlled trial, conducted over a single rotavirus season in 325 infants who were 2 to 8 months old at enrollment. Subjects were randomized to receive either placebo or WI79-9 virus vaccine at 10(7.3) plaque-forming units in three oral doses each separated by 2 months. Subjects were followed for 7 days after each dose for occurrence of adverse events and during the subsequent winter for development of rotavirus gastroenteritis. Administration of WI79-9 virus vaccine was well-tolerated, and the rates of low grade fever after each dose were no higher in vaccine recipients (8 to 21%) than in placebo recipients (14 to 19%). The protective efficacy of the WI79-9 vaccine during a subsequent epidemic of predominantly serotype G1 rotavirus was 87.0% (95% confidence limits, 62.6 to 95.5%) against relatively severe rotavirus gastroenteritis (rotavirus gastroenteritis with a clinical severity score of > 8) and was 64.1% (95% confidence limits 35.9 to 79.9%) against all symptomatic rotavirus episodes. The WI79-9 vaccine was safe and effective in prevention of homotypic human rotavirus infection in infants. Further studies of reassortant vaccines based on the bovine WC3 rotavirus should be performed.

Respiratory viral infections in the elderly.

Viral respiratory infections represent a significant challenge for those interested in improving the health of the elderly. Influenza continues to result in a large burden of excess morbidity and mortality. Two effective measures, inactivated influenza vaccine, and the antiviral drugs rimantadine and amantadine, are currently available for control of this disease. Inactivated vaccine should be given yearly to all of those over the age of 65, as well as younger individuals with high-risk medical conditions and individuals delivering care to such persons. Live, intranasally administered attenuated influenza vaccines are also in development, and may be useful in combination with inactivated vaccine in the elderly. The antiviral drugs amantadine and rimantadine are effective in the treatment and prevention of influenza A, although rimantadine is associated with fewer side-effects. Recently, the inhaled neuraminidase inhibitor zanamivir, which is active against both influenza A and B viruses, was licensed for use in uncomplicated influenza. The role of this drug in treatment and prevention of influenza in the elderly remains to be determined. Additional neuraminidase inhibitors are also being developed. In addition, to influenza, respiratory infections with respiratory syncytial virus, parainfluenza virus, rhinovirus, and coronavirus have been identified as potential problems in the elderly. With increasing attention, it is probable that the impact of these infections in this age group will be more extensively documented. Understanding of the immunology and pathogenesis of these infections in elderly adults is in its infancy, and considerable additional work will need to be performed towards development of effective control measures.

Viral respiratory infections in the institutionalized elderly: clinical and epidemiologic findings.

OBJECTIVE: To prospectively evaluate the incidence and impact of viral respiratory infection in the institutionalized elderly during a winter season. DESIGN: Prospective descriptive study, without intervention. METHOD: Patients with respiratory illnesses were evaluated by a directed history and physical examination. Nasopharyngeal secretions for viral culture were obtained, and acute and convalescent serum samples were obtained for analysis. Serologic evidence of infection with respiratory syncytial virus (RSV) and parainfluenza were determined by enzyme immunoassay (EIA), and influenza by hemagglutination-inhibition assay and EIA. SETTING: A 591-bed nursing home. PARTICIPANTS: Residents with signs or symptoms of acute respiratory illness (nasal congestion, pharyngitis, cough, wheezing, or respiratory difficulty) were eligible for study. RESULTS: A viral etiology was documented in 62 out of 149 illnesses (42%). RSV was the most common virus associated with illness; it was documented in 27% of respiratory illnesses, followed by rhinovirus (9%), parainfluenza (6%), and influenza (1%). RSV was associated with significantly more severe disease when compared with rhinovirus. Clustering of specific viral infections occurred, suggesting nosocomial transmission. CONCLUSIONS: Viruses are an important cause of acute respiratory infections in the institutionalized elderly during the winter months.

Acute respiratory tract infection in daycare centers for older persons.

OBJECTIVE: To evaluate the rate of specific pathogens and clinical syndromes associated with acute respiratory tract infections (ARTI) in frail older persons attending daycare. DESIGN: Prospective descriptive study, without intervention. SETTING: Two sites of a senior daycare program providing all-inclusive care for the older persons in Rochester, New York. PARTICIPANTS: Staff members and participants of the day-care. MEASUREMENTS: Demographic, medical, and physical findings were collected from older subjects at baseline and while ill with respiratory illnesses. Nasopharyngeal specimens for viral and Chlamydia culture and sputum for bacterial culture were obtained from subjects when ill. Acute and convalescent sera were also collected with each illness and examined for viral, chlamydial, and mycoplasma infection. MAIN RESULTS: One hundred sixty-five illnesses were documented in 165 older daycare participants as well as 113 illnesses among 67 staff members during the 15-month study. The rate of ARTI in the elderly group was 10.8 per 100 person months. The most common etiologies in both the staff and elderly participants were respiratory syncytial virus (RSV), Influenza A, and coronavirus. The etiologies of illnesses in the staff compared with those in elderly group were similar except that bacterial infections were significantly more common among the elderly (7% vs. 0, P = 0.05). Multiple pathogens were found to cocirculate within centers, and no clear outbreak of a predominant organism was noted. Cough and nasal congestion characterized most illnesses. The elderly experienced significantly more cough, dyspnea, and sputum production than did the staff. There were 10 hospitalizations related to respiratory infections and four deaths during the acute illness among the elderly group and none in staff.

Economic impact of pertussis.

OBJECTIVE: To assess the economic consequences of pertussis in Monroe County, New York (population, 713969), during a 6-year period (1989-1994). METHODS: Cases of pertussis were identified retrospectively by passive reporting and diagnosis based on culture, positive results of direct fluorescent antibody testing, or Centers for Disease Control and Prevention clinical criteria (cough for > 14 days otherwise unexplained or for > 7 days with paroxysms or whoop epidemiologically linked to a laboratory-confirmed case). One hundred seven (50%) of 216 subjects with identified cases of pertussis completed questionnaires and had medical records reviewed to ascertain the costs of illness, including physician office visits, laboratory tests, medications, hospitalization, emergency department visits, additional child care, and lost days from school (children) or from work (parents or adult cases). RESULTS: Ninety-three (87%) of the pertussis case occurred in children. The average duration of illness before diagnosis was 21.3 days (range, 12-37 days). One hundred one patients (94%) saw a physician at least once; overall, the average number of visits per case was 3.2 (range, 1-15). Ninety-seven patients (91%) received at least 1 course of antibiotic therapy (average cost for all antibiotics, $95/case), and all took symptomatic treatment (average cost, $48/case). Fifteen patients (14%) required hospitalization; average cost per admission was $13425 (range, $1732-$69637). Thirty patients (28%) were seen in emergency departments; average cost was $202 (range, $69-$289). Additional child care costs ranged from $12 to $2688. For 50 families, 1 adult lost workdays because of illness or to provide child care for an average of 8.3 days (range, 1-45 days). For 4 families, 2 adults lost an average of 44 days from work (range, 10-120 days). The cumulative number of lost workdays was 758 in association with the 107 cases of pertussis. The average full recovery time from illness was 72.9 days (range, 25-115 days). CONCLUSIONS: Total direct and indirect cost for 107 cases of pertussis in Monroe County was $381052. The economic burden of pertussis is substantial and encourages broader use of vaccination to prevent disease.

WC3 reassortant vaccines in children.

Bovine rotavirus strain WC3 (P7[5], G6) administered at the 12th passage level was well tolerated clinically in infants and efficiently induced serum virus neutralizing antibody (VNA) with bovine rotavirus G6 specificity. The protective efficacy of WC3 vaccine against all rotavirus disease was inconsistent, varying in four separate trials from 76% to 0%; some selective protection against severe disease was seen in all trials. WC3 reassortants containing the gene for an individual human rotavirus VP7 (G) or VP4 (P) surface antigen were also well tolerated, but preferentially induced VNA to the WC3 parent. Efficacy trials of human G1 VP7 reassortant WI79-9 (P7[5], G1) consistently led to > 60% protection against all rotavirus disease. A quadrivalent WC3 reassortant vaccine was developed to contain four separate monovalent reassortants expressing human rotaviruses surface proteins G1, G2, G3, and P1A [8] respectively. In a multicenter trial including 439 infants, this vaccine induced 67.1% protection against all rotavirus disease (defined as positive for rotavirus antigen by ELISA only [p = < 0.001]) and 72.6% protection when the standard for rotavirus diagnosis was a positive test of stool for both rotavirus antigen by ELISA and rotavirus RNA by electropherotype analysis (p = < 0.001). In this trial, episodes of the most severe rotavirus disease (clinical severity score > 16.0 eight cases) occurred only in placebo recipients.

Development of an enzyme immunoassay for the Hawaii agent of viral gastroenteritis.

The Hawaii agent is a Norwalk-like virus of acute gastroenteritis in humans which is antigenically distinct from the prototype Norwalk agent. We established a solid phase sandwich type microtiter enzyme immunoassay (EIA) for Hawaii antigen employing sera and stools from experimentally challenged volunteers as reagents. This assay detected the Hawaii agent in stools from 3 of 8 volunteers who were ill after oral challenge with the Hawaii agent, including one specimen which was positive to a dilution of 1/320. Virus shedding occurred on days 3 to 7 after challenge. The Hawaii-positive stools did not react in the EIAs for Norwalk and Snow Mountain agent (SMA), nor did Norwalk or SMA-positive stools react in the Hawaii EIA. Human rotavirus, enteric adenovirus, feline calicivirus, and several enteroviruses also did not react in the Hawaii EIA. A blocking EIA to detect serum antibody to the Hawaii agent was also developed employing a diarrheal stool containing Hawaii as a source of antigen. Serum antibody rises were detected in 15 of 16 individuals with experimentally induced illness after challenge and in 3 of 5 individuals who remained well after challenge. The EIA for the Hawaii agent should permit epidemiologic studies of the Hawaii agent to be carried out as well as allow further characterization of the Hawaii virion.

Normal beta-NGF content in Alzheimer's disease cerebral cortex and hippocampus.

Nerve growth factor (beta-NGF) is known to have beneficial effects on cholinergic cell survival and to function both in vivo and in vitro. It has been speculated that this protein, or the lack of it, may be involved in the aetiology of Alzheimer's disease (AD). We describe the measurement of beta-NGF content in 4 regions of the cerebral cortex and the hippocampus in AD brain compared with brain tissue from age-matched normal subjects using a sensitive sandwich immunoassay (ELISA). There was no difference in beta-NGF content in any region examined in AD compared with normal values despite the marked loss of cortical cholinergic function.

Low affinity nerve growth factor receptor binding in normal and Alzheimer's disease basal forebrain.

The binding characteristics of radiolabelled beta-nerve growth factor ([125I]NGF) have been determined on membrane preparations of basal forebrain from Alzheimer's disease (AD) brain and age-matched normal brains. [125I]NGF binds in a specific fashion indicative of a single receptor and is not displaced with microM concentrations of cytochrome c, insulin or epidermal growth factor (EGF). The mean dissociation constant (Kd) and the mean capacity (Bmax) of the NGF receptor were not significantly different between the 5 AD and 5 normal basal forebrain samples examined. Choline acetyltransferase (ChAT) activity was significantly reduced (P less than or equal to 0.001) in AD cerebral cortical samples compared with normal tissue.