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Alzheimer's disease (AD) is characterized by retrograde memory deficits primarily caused by dysfunction of the hippocampal complex. Unresolved questions exist concerning the time course of hippocampal involvement in conscious recollection of declarative knowledge, as reports of temporal gradients of retrograde amnesia have been inconclusive. The aim of this study was to examine whether the extent and severity of retrograde amnesia is mediated by retrieval frequency or, in contrast, whether it depends on the age of the memory according to the assumptions of the main current theories of memory formation. We compared recall of past public events in patients with AD and healthy control (HC) individuals using the Historic Events Test (HET). The HET assesses knowledge about famous public events of the past 60 years divided into four time segments and consists of subjective memory rating, dating accuracy, and contextual memory tasks. Although memory for public events was impaired in AD patients, there was a strong effect of retrieval frequency across all time segments and both groups. As AD and HC groups derived similar benefits from greater retrieval frequency, cortical structures other than the hippocampal complex may mediate memory retrieval. These findings suggest that more frequently retrieved events and facts become more independent of the hippocampal complex and thus better protected against early damage of AD. This could explain why cognitive activity may delay the onset of memory decline in persons who develop AD.

Background Alzheimer's disease (AD) has been linked to a state of cerebral and systemic inflammation. The objective of the present study was to determine whether singular markers or a set of inflammatory biomarkers in peripheral blood allow discrimination between AD patients and healthy controls at the individual level. Methods Using bead based multiplexed sandwich immunoassays, 25 inflammatory biomarkers were measured in 164 serum samples from individuals with early AD and age-matched cognitively healthy elderly controls. The data set was randomly split into a training set for feature selection and classification training and a test set for class prediction of blinded samples (1 : 1 ratio) to evaluate the chosen predictors and parameters. Multivariate data analysis was performed with use of a support vector machine (SVM). Results After selection of sTNF-R1 as most discriminative parameter in the training set, the application of SVM to the independent test dataset resulted in a 90.0% correct classification for individual AD and control subjects. Conclusions We identified sTNF-R1 from a marker set consisting of 25 inflammatory biomarkers, which allowed SVM-based discrimination of AD patients from healthy controls on a single-subject classification level comparably well as biomarker panels with a clinically relevant accuracy and validity. Although larger sample populations will be needed to confirm this diagnostic accuracy, our study suggests that sTNF-R1 in serum-either as singular marker or incorporated into a biomarker panel-could be a powerful new biomarker for detection of AD. In addition, selective inhibition of TNF-R1 function may represent a new therapeutic approach in AD.

Plasma levels of amyloid-β (Aβ) peptides are potential biomarkers of early cognitive impairment and of Alzheimer's disease (AD) risk. However, the association of Aβ peptides with the rate of cognitive decline in AD patients is still unclear. In the present study we demonstrate that Aβ₁₋₄₂ plasma levels show a significant correlation with the rate of cognitive decline and are significantly increased in AD patients with fast cognitive decline (decrease of Mini-Mental Status Examination (MMSE) score ≥ 5/year; n = 12) compared to AD patients with slow cognitive decline (decrease of MMSE score ≤ 4/year; n = 28), independent of baseline MMSE scores, age and cholinesterase inhibitor intake, but dependent on history of myocardial infarction and history of stroke in a multivariate analysis. These results suggest that Aβ₁₋₄₂ plasma levels are associated with the rate of cognitive decline in AD patients and may be influenced by atherosclerotic vasculopathies such as stroke and myocardial infarction.

Alzheimer's disease (AD) is characterized by massive neuronal cell loss in the brain. Granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor that promotes neuroprotective effects and supports neurogenesis in the brain. In the present study, we found significantly lower G-CSF plasma levels in 50 early AD patients in comparison with 50 age-matched healthy controls. In AD patients, G-CSF levels showed a significant inverse correlation with amyloid-beta (Abeta1-42) levels in cerebrospinal fluid, but not with levels of tau protein in cerebrospinal fluid or Mini-Mental Status Examination scores. In addition, G-CSF plasma levels were significantly inversely correlated with age in AD patients and healthy controls. In conclusion, decreased G-CSF plasma levels in early AD patients may contribute to a deficient hematopoietic brain support with putative pathogenic relevance. Further studies are needed to examine whether a modulation of hematopoietic growth factors such as G-CSF could be a promising new therapeutic strategy for AD.

Preclinical and clinical studies gave evidence that lithium could be useful in the treatment of Alzheimer's disease (AD). In experimental investigations, lithium induces brain-derived neurotrophic factor (BDNF). Recent studies have found a decrease of BDNF in the serum and brains of AD patients with potentially consecutive lack of neurotrophic support. We assessed the influence of a lithium treatment on BDNF serum concentration in a subset of a greater sample recruited for a randomized, single-blinded, placebo-controlled, parallel-group multicenter 10-week study, investigating the efficacy of lithium treatment in AD patients. In AD patients treated with lithium, a significant increase of BDNF serum levels, and additionally a significant decrease of ADAS-Cog sum scores in comparison to placebo-treated patients, were found. Diminution of cognitive impairment was inversely correlated with lithium serum concentration. Upregulation of BDNF might be part of a neuroprotective effect of lithium in AD patients. The results of the present investigation encourage performing studies with longer treatment phases to observe potential positive long-term effects of lithium in AD patients.

Alzheimer's disease (AD) is characterized by massive neuronal cell loss in the brain. Stem cell factor (SCF) is a hematopoietic growth factor (HGF) that promotes neuroprotective effects and supports neurogenesis in the brain. In the present study, we found significantly lower SCF plasma levels in 30 early AD patients (908.5 +/- 181.7 pg/ml) in comparison with 30 age-matched healthy controls (1058.3 +/- 221.5 pg/ml; p = 0.006). SCF plasma levels in AD patients showed a significant inverse correlation with dementia severity as measured by ADAS-Cog (r = -0.289; p = 0.037). AD patients showed significantly lower SCF levels in cerebrospinal fluid (CSF) (131.60 +/- 43.03 pg/ml) in comparison with 15 age- and gender-matched patients with other non-inflammatory neurological disease (NIND) (166.03 +/- 42.5 pg/ml; p = 0.017). In addition, we found significant positive correlations between SCF and CXCL12 (also known as SDF-1) plasma levels in healthy controls (r = 0.341; p = 0.008) and between SCF and CXCL12 CSF levels in AD patients (r = 0.487; p < 0.001). In conclusion, decreased SCF plasma and CSF levels in early AD patients may contribute to a deficient hematopoietic brain support with putative pathogenic and clinical relevance. Further studies are needed to examine whether a manipulation of HGFs such as SCF could be a promising new therapeutic strategy for AD.