Pay for performance associated with increased volume of medication reviews but not with less inappropriate use of medications among the elderly - an observational study.

OBJECTIVE: A pay for performance programme was introduced in 2009 by a Swedish county with 1.6 million inhabitants. A process measure with payment linked to coding for medication reviews among the elderly was adopted. We assessed the association with inappropriate medication for five years after baseline. DESIGN AND SETTING: Observational study that compared medication for elderly patients enrolled at primary care units that coded for a high or low volume of medication reviews. PATIENTS: 144,222 individuals at 196 primary care centres, age 75 or older. MAIN OUTCOME MEASURES: Percentage of patients receiving inappropriate drugs or polypharmacy during five years at primary care units with various levels of reported medication reviews. RESULTS: The proportion of patients with a registered medication review had increased from 3.2% to 44.1% after five years. The high-coding units performed better for most indicators but had already done so at baseline. Primary care units with the lowest payment for coding for medication reviews improved just as well in terms of inappropriate drugs as units with the highest payment - from 13.0 to 8.5%, compared to 11.6 to 7.4% and from 13.6 to 7.2% vs 11.8 to 6.5% for polypharmacy. CONCLUSIONS: Payment linked to coding for medication reviews was associated with an increase in the percentage of patients for whom a medication review had been registered. However, the impact of payment on quality improvement is uncertain, given that units with the lowest payment for medication reviews improved equally well as units with the highest payment.

Antidepressants and mortality risk in a dementia cohort: data from SveDem, the Swedish Dementia Registry.

BACKGROUND: The association between mortality risk and use of antidepressants in people with dementia is unknown. OBJECTIVE: To describe the use of antidepressants in people with different dementia diagnoses and to explore mortality risk associated with use of antidepressants 3 years before a dementia diagnosis. METHODS: Study population included 20 050 memory clinic patients from the Swedish Dementia Registry (SveDem) diagnosed with incident dementia. Data on antidepressants dispensed at the time of dementia diagnosis and during 3-year period before dementia diagnosis were obtained from the Swedish Prescribed Drug Register. Cox regression models were used. RESULTS: During a median follow-up of 2 years from dementia diagnosis, 25.8% of dementia patients died. A quarter (25.0%) of patients were on antidepressants at the time of dementia diagnosis, while 21.6% used antidepressants at some point during a 3-year period before a dementia diagnosis. Use of antidepressant treatment for 3 consecutive years before a dementia diagnosis was associated with a lower mortality risk for all dementia disorders and in Alzheimer's disease. CONCLUSION: Antidepressant treatment is common among patients with dementia. Use of antidepressants during prodromal stages may reduce mortality in dementia and specifically in Alzheimer's disease.

Cognitive deficits in unipolar old-age depression: a population-based study.

BACKGROUND: There is substantial variability in the degree of cognitive impairment among older depressed persons. Inconsistencies in previous findings may be due to differences in clinical and demographic characteristics across study samples. We assessed the influence of unipolar depression and severity of depression on cognitive performance in a population-based sample of elderly persons aged ⩾60 years. METHOD: Eighty-nine persons fulfilled ICD-10 criteria for unipolar depression (mild, n = 48; moderate, n = 38; severe, n = 3) after thorough screening for dementia (DSM-IV criteria), psychiatric co-morbidities and antidepressant pharmacotherapy. Participants (n = 2486) were administered an extensive cognitive test battery. RESULTS: Moderate/severe unipolar depression was associated with poorer performance on tasks assessing processing speed, attention, executive function, verbal fluency, episodic memory and vocabulary. Mild depression was associated with poorer performance in processing speed, and few differences between mild and moderate/severe depression were observed. No association between depression and short-term memory, general knowledge or spatial ability was observed. Increasing age did not exacerbate the depression-related cognitive deficits, and the deficits remained largely unchanged after excluding persons in a preclinical phase of dementia. Furthermore, depression-related cognitive deficits were not associated with other pharmacological treatments that may affect cognitive performance. CONCLUSIONS: Cognitive deficits in unipolar old-age depression involve a range of domains and the cognitive deficits seem to follow the spectrum of depression severity. The finding that mild depression was also associated with poorer cognitive functioning underscores the importance of detecting mild depression in elderly persons.

Undertreatment of osteoporosis in persons with dementia? A population-based study.

UNLABELLED: In this population-based study of more than 2,600 elderly, people with dementia received less preventive treatment for osteoporosis compared to people without dementia, although osteoporotic fractures were more common in patients with dementia. Thus, our results indicate an undertreatment of osteoporosis in dementia. INTRODUCTION: This study compares the use of osteoporosis drugs in elderly with and without dementia, taking into account osteoporotic fractures and type of housing. METHODS: We analyzed data from the baseline examination (2001-2004) of The Swedish National Study on Aging and Care- Kungsholmen (SNAC-K), Stockholm, Sweden. Participants were aged ≥ 66 years (n = 2610). We analysed the use of bisphosphonates, raloxifene, and calcium/vitamin D combinations in relation to clinically based dementia diagnosis. Information about osteoporotic fractures during the previous 4 years was obtained from the Swedish National Patient Register. We used logistic regression to analyze the association between dementia status and use of osteoporosis drugs. RESULTS: Osteoporosis drugs (mainly calcium/vitamin D combinations) were used by 5% of the persons with dementia and 12% of the persons without dementia. Furthermore, 25% of the persons with dementia and 7% of the persons without dementia had had at least one osteoporotic fracture during the past 4 years. After controlling for age, sex, osteoporotic fractures, and type of housing (own home or institution), persons with dementia were less likely to use osteoporosis drugs than persons without dementia (OR = 0.34; 95% CI, 0.19-0.59). CONCLUSIONS: Our results indicate an undertreatment of osteoporosis in persons with dementia, although osteoporotic fractures are common among these patients.

Trends in polypharmacy and potential drug-drug interactions across educational groups in elderly patients in Sweden for the period 1992 - 2002.

OBJECTIVE: This study investigates the changes in drug use, polypharmacy and potential drug-drug interactions (DDIs) between educational groups of Swedish elderly over a 10-year period from 1992 - 2002. METHODS: We used data from SWEOLD I (n = 512) from 1992 and SWEOLD II from 2002 (n = 561), which are nationally representative surveys of the elderly population in Sweden aged 77 years and older. Both community-based and institutionalized persons were included. Information on drug use was based on personal interviews and all drugs used in the two weeks prior to the studies were recorded. The three outcomes under study were drug use, polypharmacy (concurrent use of five or more drugs), and potential DDIs. RESULTS: In the SWEOLD data from 1992 - 2002, the mean number of drugs used per person increased from 2.5 - 4.4. Overall, 81% of the study participants were drug users in 1992 as compared to 88% in 2002. The prevalence of polypharmacy increased 3-fold (from 18% in 1992 to 42% in 2002) after controlling for age and gender. In both SWEOLD surveys, the less educated reported polypharmacy more often (19% in 1992 and 46% in 2002) than the higher educated (12% in 1992 and 36% in 2002). Potential DDIs also increased, both among the less educated (14% in 1992 to 26% in 2002) and the higher educated (18% in 1992 to 24% in 2002). The most pronounced changes in the consumption of specific drug groups were observed in antithrombotic agents, beta-blocking agents, ACE inhibitors, and vitamin B12 and folic acid. In general, the use of most therapeutic classes increased more among the well educated compared to less educated men between 1992 and 2002, whereas the opposite relationship prevailed among women. CONCLUSION: This study indicates that the use of drugs, polypharmacy and potential DDIs have increased during 1992 to 2002 among the elderly. These changes were most prominent among the less educated women. Polypharmacy and potential DDIs represent potential health hazards for the elderly. Therefore, the trends of increasing polypharmacy and drug-drug interactions deserve attention and the mechanisms behind should be investigated further.

Aspirin, NSAIDs, risk of dementia, and influence of the apolipoprotein E epsilon 4 allele in an elderly population.

In a cohort study, 1,301 subjects free of dementia at baseline in the Kungsholmen Project were followed up to 6 years. We studied the association between use of aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), incidence of Alzheimer's disease (AD) and overall dementia, and the influence of the apolipoprotein E epsilon4 allele. In stratified analyses, a relative risk (RR) of 1.80 (95% CI 1.14-2.83) for AD was seen, in the apoE epsilon4-negative group using aspirin. This implicates a possible different mechanism of developing AD in this group. We also found a possible protective effect of NSAIDs against AD, since no one who used NSAIDs for around 3 years had developed AD 3 years later. One user developed vascular dementia, and a low point value of risk was seen, however, not significant (RR 0.23; 95% CI 0.03-1.68). This could be due to the small samples in our study, or to comorbidity contributing to the development of dementia in this elderly population.

Beta-secretase-cleaved amyloid precursor protein in Alzheimer brain: a morphologic study.

beta-amyloid (Abeta) is the main constituent of senile plaques seen in Alzheimer's disease. Abeta is derived from the amyloid precursor protein (APP) via proteolytic cleavage by proteases beta- and gamma-secretase. In this study, we examined content and localization of beta-secretase-cleaved APP (beta-sAPP) in brain tissue sections from the frontal, temporal and occipital lobe. Strong granular beta-sAPP staining was found throughout the gray matter of all three areas, while white matter staining was considerably weaker. beta-sAPP was found to be localized in astrocytes and in axons. We found the beta-sAPP immunostaining to be stronger and more extensive in gray matter in Alzheimer disease (AD) cases than controls. The axonal beta-sAPP staining was patchy and unevenly distributed for the AD cases, indicating impaired axonal transport. beta-sAPP was also found surrounding senile plaques and cerebral blood vessels. The results presented here show altered beta-sAPP staining in the AD brain, suggestive of abnormal processing and transport of APP.

Cognitive performance in very old diabetic persons: the impact of semantic structure, preclinical dementia, and impending death.

The authors examined the associations of diabetes mellitus with cognitive performance in a population-based sample of nondemented and nondepressed very old persons. Diabetic participants (n = 31) were compared with nondiabetic controls (n = 307), adjusting for age, educational level, and related vascular diseases and signs. Results showed that diabetic persons performed significantly worse on tests of verbal fluency and episodic memory but that the effects on both types of abilities were less pronounced in tasks involving higher degrees of semantic structure. Follow-up analyses further revealed that preclinical dementia and impending death accounted for much of the observed associations. The results suggest that cognitive deficits among very old diabetics are most likely detected by tasks that draw less on semantic structures and that the most robust effects may be found in letter fluency performance.

Loss of stimulatory effect of guanosine triphosphate on [(35)S]GTPgammaS binding correlates with Alzheimer's disease neurofibrillary pathology in entorhinal cortex and CA1 hippocampal subfield.

Heterotrimeric guanosine triphosphate (GTP)-binding proteins (G-proteins) couple many different cell surface receptor types to intracellular effector mechanisms. Uncoupling between receptors and G-proteins and between G-proteins and adenylyl cyclase (AC) and phospholipase C (PLC) has been described for Alzheimer's disease (AD) brain. However, there is little information on whether altered G-protein signaling in AD is just an end-stage phenomenon or is important for the progression of disease pathology. Here we used [(35)S]GTPgammaS autoradiography to study G-protein distribution in sections of entorhinal cortex and hippocampus from 23 cases staged for neurofibrillary changes and amyloid deposits according to Braak and Braak (Acta Neuropathol. [1991] 82:239-259). We also studied the effects of GTP, which has been found to increase [(35)S]GTPgammaS binding in an Mg(2+)-dependent manner. Results show that the ability of GTP (3 microM) to stimulate [(35)S]GTPgammaS binding declined significantly with staging for neurofibrillary changes in the entorhinal cortex (P < 0.05, ANOVA) and CA1 subfield of the hippocampus (P < 0.05, ANOVA). No significant changes were seen for [(35)S]GTPgammaS binding in the absence of GTP. Our results suggest a decrease in G-protein GTP hydrolysis, which correlates with the progression of AD neurofibrillary changes, in the regions most affected by this pathology. These alterations appear to occur prior to stages corresponding to clinical disease and could lead to an impaired regulation of several signaling systems in AD brain.

Psychotropic drug use in elderly people with and without dementia.

OBJECTIVE: To determine the prevalence of psychotropic drug use in very old persons with and without dementia in two time periods, and describe the patterns of psychotropic drug use between institutions and non-institutions. METHODS: Descriptive analysis on a sample of subjects aged 81+ from a population-based study in Stockholm, Sweden. Psychotropic drug use data were collected from the 1987-1989 and 1994-1996 periods of the study. The diagnosis of dementia was based on the DSM III-R. RESULTS: About 41% of the subjects used at least one psychotropic drug in both periods. Women and subjects in institutions more commonly used psychotropic drugs. The most commonly reported were, in rank order, hypnotics-sedatives, anxiolytics, antipsychotics and antidepressants. Hypnotics-sedatives and anxiolytics were the most commonly used in both institutions and non-institutions. More persons with dementia used psychotropic drugs in both periods. The use of newer drugs, for example, SSRI, was evident. Multivariate analyses showed increased risk for psychotropic drug use among subjects in institutions. CONCLUSIONS: This study confirms the high rate of psychotropic drug use in the very old, particularly in persons with dementia. Psychotropic drug use was high among subjects living in institutions.

Receptor-G-protein signalling in Alzheimer's disease.

Based on radioligand binding studies, it has long been assumed that the neurochemical pathology of Alzheimer's disease (AD) does not involve widespread changes in post-synaptic neurotransmitter function. However, more recent studies suggest that receptor function in AD may be compromised due to disrupted post-receptor signal transduction, in particular that mediated by the G-protein regulated phosphoinositide hydrolysis and adenylate cyclase (AC) pathways. The phosphoinositide hydrolysis pathway has been shown to be altered at a number of levels in AD post-mortem brains, including impaired agonist and G-protein regulation of phospholipase C, decreased protein kinase C (PKC) levels and activity, and a reduced number of receptor sites for the second messenger, Ins(1,4,5)P3. Of these, loss of Ins(1,4,5)P3 receptors and PKC in the entorhinal cortex and hippocampus correlates with AD-related neurofibrillary changes, as staged according to Braak's protocol. Disregulation of the phosphoinositide hydrolysis pathway may therefore have consequences for the progression of AD pathology. In contrast to the extensive pattern of disruption seen with the phosphoinositide hydrolysis pathway, changes to AC signalling in AD appear more circumscribed. Disruptions include a lesion at the level of Gs-protein stimulation of AC and, at least in the hippocampus, reduced enzyme activities in response to forskolin stimulation. Of these, the latter change has been shown to precede neurofibrillary changes. Apart from a loss of calcium/calmodulin sensitive AC isoforms, other components of this signalling pathway, including G-protein levels, Gi-protein mediated inhibition and protein kinase A levels and activity, remain relatively preserved in the disorder.

Dysfunctional intracellular calcium homoeostasis: a central cause of neurodegeneration in Alzheimer's disease.

The clinical symptoms of all forms of Alzheimer's disease (AD) result from a slowly progressive neurodegeneration that is associated with the excessive deposition of beta-amyloid (A beta) in plaques and in the cerebrovasculature, and the formation of intraneuronal neurofibrillary tangles, which are composed primarily of abnormally hyperphosphorylated tau protein. The sequence of cellular events that cause this pathology and neurodegeneration is unknown. It is, however, most probably linked to neuronal signal transduction systems that become misregulated in the brains of certain individuals, causing excessive A beta to be formed and/or deposited, tau to become aggregated and hyperphosphorylated and neurons to degenerate. We hypothesize that a progressive alteration in the ability of neurons to regulate intracellular calcium, particularly at the level of the endoplasmic reticulum, is a crucial signal transduction event that is linked strongly to the initiation and development of AD pathology. In this chapter we will discuss the key findings that lend support to this hypothesis.

Vitamin B(12) and folate in relation to the development of Alzheimer's disease.

OBJECTIVE: To explore the associations of low serum levels of vitamin B(12) and folate with AD occurrence. METHODS: A population-based longitudinal study in Sweden, the Kungsholmen PROJECT: A random sample of 370 nondemented persons, aged 75 years and older and not treated with B(12) and folate, was followed for 3 years to detect incident AD cases. Two cut-off points were used to define low levels of vitamin B(12) (< or =150 and < or =250 pmol/L) and folate (< or =10 and < or =12 nmol/L), and all analyses were performed using both definitions. AD and other types of dementia were diagnosed by specialists according to DSM-III-R criteria. RESULTS: When using B(12) < or =150 pmol/L and folate < or =10 nmol/L to define low levels, compared with people with normal levels of both vitamins, subjects with low levels of B(12) or folate had twice higher risks of developing AD (relative risk [RR] = 2.1, 95% CI = 1.2 to 3.5). These associations were even stronger in subjects with good baseline cognition (RR = 3.1, 95% CI = 1.1 to 8.4). Similar relative risks of AD were found in subjects with low levels of B(12) or folate and among those with both vitamins at low levels. A comparable pattern was detected when low vitamin levels were defined as B(12) < or =250 pmol/L and folate < or =12 nmol/L. CONCLUSIONS: This study suggests that vitamin B(12) and folate may be involved in the development of AD. A clear association was detected only when both vitamins were taken into account, especially among the cognitively intact subjects. No interaction was found between the two vitamins. Monitoring serum B(12) and folate concentration in the elderly may be relevant for prevention of AD.

[Increased consumption of drugs among the elderly results in greater risk of problems]. / Okat läkemedelsintag bland äldre innebär ökad risk för problem.

With aging comes an increasing prevalence of diseases and symptoms that frequently require pharmaceutical treatment. However, aging also brings about bodily changes that result in increased effects and prolonged action of many drugs. Multiple drug use--often termed polypharmacy--seen in many elderly individuals, is the most important risk factor for adverse drug reactions (ADR) and increases the risk of drug interactions and poor compliance. ADR's are responsible for about 10% of all hospital admissions of elderly patients. The drugs most commonly involved are cardiovascular, psychotropics and anti-inflammatory agents. Many of these ADR's are dose-dependent and preventable. Drug use has increased over the last few years, largely thanks to the availability of new and effective agents. This calls for increased vigilance and prudence in prescribing for the elderly.

The appropriateness of drug use in an older nondemented and demented population.

OBJECTIVE: To assess the extent of inappropriateness of drug use in an older nondemented and demented population. DESIGN: Descriptive analysis based on data from a sample of older subjects age 81 years and older. Data were collected from the second follow-up conducted in 1994-1996. SETTING: A population-based study of the Kungsholmen project in Stockholm, Sweden. PARTICIPANTS: Drug information was obtained from 681 subjects with a mean age of 86.9 years. The subjects were predominantly women (78%). Thirteen percent resided in institutions and 27.6% were diagnosed with dementia. MEASUREMENTS: Dementia diagnosis based on DSM III-R. Criteria for inappropriateness of drug use: use of drugs with potent anticholinergic properties, drug duplication, potential drug-drug and drug-disease interactions, and inappropriate drug dosage. RESULTS: The mean number of drugs used was 4.6: 4.5 drugs for nondemented and 4.8 for demented subjects. Nondemented subjects more commonly used cardiovascular-system drugs and demented subjects used nervous-system drugs. Demented subjects were more commonly exposed to drug duplication and to drugs with potent anticholinergic properties, both involving the use of psychotropic drugs. Nondemented subjects were more commonly exposed to potential drug-disease interactions, mostly with the use of cardiovascular drugs. The most common drug combination leading to a potential interaction was the use of digoxin with furosemide, occurring more frequently among nondemented subjects. The most common drug-disease interaction was the use of beta-blockers and calcium antagonists in subjects with congestive heart failure. The doses of drugs taken by both nondemented and demented subjects were mostly lower than the defined daily dose. CONCLUSION: There was substantial exposure to presumptive inappropriateness of drug use in this very old nondemented and demented population. The exposure of demented subjects to psychotropic drugs and nondemented subjects to cardiovascular drugs reflect the high frequency of prescribing these drugs in this population.

Apolipoprotein E genotypes and the incidence of Alzheimer's disease among persons aged 75 years and older: variation by use of antihypertensive medication?

The authors examined the impact of the apolipoprotein E (APOE)(*)epsilon4 allele on Alzheimer's disease incidence in relation to use of antihypertensive medication. A population-based (Kungsholmen Project) cohort of 985 nondemented Swedish subjects aged >/=75 years was followed for an average of 3 years (1990-1992); 164 dementia (122 Alzheimer's disease) cases were identified. Compared with (*)epsilon3/(*)epsilon3, the APOE(*)epsilon4 allele increased the risk of developing dementia (relative risk (RR) = 1.5, 95% confidence interval (CI): 1.1, 2.1) and Alzheimer's disease (RR = 1.7, 95% CI: 1.2, 2.5). Subjects using antihypertensive medication at baseline (n = 432, 80% used diuretics) had a decreased risk of dementia (RR = 0.6, 95% CI: 0.5, 0.9) and Alzheimer's disease (RR = 0.5, 95% CI: 0.3, 0.8) after adjustment for several variables, including APOE. The effect of antihypertensive medication use was more pronounced among (*)epsilon4 carriers. For those not using antihypertensive medication, the relative risks of dementia and Alzheimer's disease for carriers were 2.2 (95% CI: 1.4, 3.4) and 2.3 (95% CI: 1.4, 3.7), respectively. The corresponding relative risks for those using antihypertensive medication were 0.9 (95% CI: 0.5, 1.6) and 1.1 (95% CI: 0.6, 2.2). The APOE(*)epsilon4 allele is an important predictor of dementia and Alzheimer's disease incidence. Further studies are needed to clarify whether use of antihypertensive medication, especially diuretics, modifies the effect of the allele.

Calcium ionophore A23187 specifically decreases the secretion of beta-secretase cleaved amyloid precursor protein during apoptosis in primary rat cortical cultures.

Alzheimer's disease (AD) is characterized by the degeneration and loss of neurons, intracellular neurofibrillary tangles and the accumulation of extracellular senile plaques consisting mainly of beta-amyloid (A beta). A beta is generated from the amyloid precursor protein (APP) by sequential beta- and gamma-secretase cleavage. Alternatively, APP may be cleaved within the A beta region by alpha-secretase, preventing A beta formation. Here we investigated APP processing and secretion in primary neurons, using either colchicine or the calcium ionophore A23187 to induce apoptosis. Cell viability was determined by MTT measurements and apoptosis was further confirmed by annexin V and propidium iodide staining. We found that exposure to A23187 significantly decreased the secretion of soluble beta-secretase cleaved APP (beta-sAPP) in a caspase-dependent manner, although the secretion of total soluble APP beta sAPP) did not change. In addition, caspase inhibition restored cell viability to control levels. Exposure to colchicine did not change the amount of either secreted beta-sAPP or total sAPP and caspase inhibition was only partially able to restore cell viability. We conclude that calcium homeostasis is an important apoptotic effector specifically affecting the beta-secretase cleavage of APP.

The relationship between signs of cardiovascular deficiency and cognitive performance in old age: a population-based study.

The influence of cardiovascular signs (CVS) on cognitive performance was examined in 227 older adults not suffering from dementia between 75 and 96 years of age who were sampled from the community. Participants received a comprehensive physical examination that included specific evaluation of current CVS, including dyspnea, cardiac murmur, and edema in lower limbs. They were administered tests of digit span, episodic recall and recognition, verbal fluency, and visuospatial skill. CVS were found to predict performance on tests of episodic memory and visuospatial skill, after the effects of age, education, gender, relevant drug use, and mood symptoms were controlled for. Although CVS accounted for relatively little general performance variation, the findings are relevant to the understanding of normal variation in late-life cognitive performance. Finally, CVS increased with age and accounted for a sizable proportion of the age-related cognitive variation.

Mild cognitive impairment in the population and physical health: data on 1,435 individuals aged 75 to 95.

BACKGROUND: The physical health correlates of mild cognitive impairment (MCI) in the older individual are poorly known. The aim of this study was to investigate the relationship between physical health and MCI with population data. METHODS: Subjects were 1,435 nondemented 75- to 95-year-old subjects. MCI was defined as scoring one standard deviation below age- and education-specific means on the Mini-Mental State Examination. MCI was consistently associated with indicators of poorer health in logistic regression models with adjustment for potential confounders. RESULTS: The adjusted odds ratios for those with two, three, four, or more somatic symptoms compared with those with one or no symptoms were 1.3 (95% confidence intervals 1.0 to 1.9) and 2.1 (1.2 to 4.5; p for trend =.004); for those with poor self-rated health the odds ratio was 1.9 (1.4 to 2.6); for those with one, two, or more chronic diseases compared with those with no chronic diseases, the odds ratios were 1.3 (0.9 to 1.9) and 3.0 (1.2 to 7.6; p for trend =.02); and for those dying during the 3-year follow-up period the odds ratio was 1.5 (1.1 to 2.2). CONCLUSIONS: MCI is associated with poor physical health, leading to the hypothesis of a causal relationship between physical diseases and MCI in older populations.

Levels of alpha- and beta-secretase cleaved amyloid precursor protein in the cerebrospinal fluid of Alzheimer's disease patients.

Alternative cleavage of the amyloid precursor protein (APP) results in generation and secretion of both soluble APP (sAPP) and beta-amyloid (Abeta). Abeta is the main component of the amyloid depositions in the brains of Alzheimer's disease (AD) patients. Using Western blotting, we compared the levels of alpha-secretase cleaved sAPP, beta-secretase cleaved sAPP and total sAPP, in cerebrospinal fluid (CSF) from 13 sporadic AD patients and 13 healthy controls. Our findings show significant amounts of beta-secretase cleaved sAPP in CSF. There was no statistically significant difference in the levels of beta-secretase cleaved sAPP between AD patients and controls. The levels of alpha-secretase cleaved sAPP and total sAPP were, however, found to be significantly lower in the AD patients than in the controls.