The microbiota–gut–brain axis plays an important role in the development of neurodegenerative diseases. Commensal and pathogenic enteric bacteria can influence brain and immune system function by the production of lipopolysaccharides and amyloid. Dysbiosis of the intestinal microbiome induces local and consecutively systemic immune-mediated inflammation. Proinflammatory cytokines then trigger neuroinflammation and finally neurodegeneration. Immune-mediated oxidative stress can lead to a deficiency of vitamins and essential micronutrients. Furthermore, the wrong composition of gut microbiota might impair the intake and metabolization of nutrients. In patients with Alzheimer’s disease (AD) significant alterations of the gut microbiota have been demonstrated. Standard Western diet, infections, decreased physical activity and chronic stress impact the composition and diversity of gut microbiota. A higher abundancy of “pro-inflammatory” gut microbiota goes along with enhanced systemic inflammation and neuroinflammatory processes. Thus, AD beginning in the gut is closely related to the imbalance of gut microbiota. Modulation of gut microbiota by Mediterranean diet, probiotics and curcumin can slow down cognitive decline and alter the gut microbiome significantly. A multi-domain intervention approach addressing underlying causes of AD (inflammation, infections, metabolic alterations like insulin resistance and nutrient deficiency, stress) appears very promising to reduce or even reverse cognitive decline by exerting positive effects on the gut microbiota.

There is strong evidence that vascular risk factors play a role in the development of Alzheimer's disease (AD) or vascular dementia (vaD). Ethanol (EtOH) and cholesterol are such vascular risk factors, and we recently showed that hypercholesterolemia causes pathologies similar to AD [Ullrich et al. (2010) Mol Cell Neurosci 45, 408–417]. The aim of this study was to investigate the effects of long-term (12 months) EtOH treatment (20% v/v in drinking water) alone or long-term 5% cholesterol diet alone or a combination (mix) in adult Sprague–Dawley rats. Long-term EtOH treatment (plasma EtOH levels 58±23 mg/dl) caused significant impairment of spatial memory, reduced the number of choline acetyltransferase- and p75 neurotrophin receptor-positive nucleus basalis of Meynert neurons, decreased cortical acetylcholine, elevated cortical monocyte chemoattractant protein-1 and tissue-type plasminogen activator, enhanced microglia, and markedly induced anti-rat immunoglobulin G-positive blood–brain barrier leakage. The effect of long-term hypercholesterolemia was similar. Combined long-term treatment of rats with 20% EtOH and 5% cholesterol (mix) did not potentiate treatment with EtOH alone, but instead counteracted some of the EtOH-associated effects. In conclusion, our data show that vascular risk factors EtOH and cholesterol play a role in cognitive impairment and possibly vaD.

Several parallels exist between platelets and the brain, which make them interesting for studying the neurobiology of psychiatric disorders, such as Alzheimer's disease, depression, schizophrenia and anxiety disorders. Platelets store, secrete and process the amyloid precursor protein which is cleaved into the β-amyloid (Aβ) peptides. The accumulation of Aβ in brain (plaques) and vessels (Aβ-angiopathy) is a major hallmark in AD. Platelets contain high amounts of serotonin and a dysfunction of the serotoninergic system is involved in the development of several behavior disorders, such as depression, anxiety disorders and self aggressive disturbances. Furthermore, platelets are able to take up dopamine and express various dopamine receptors, which make them to an interesting tool to study the underlying mechanisms of schizophrenia. In summary, platelets are an interesting and easily accessible cell type to study changes related to different psychiatric disorders and platelets proteins may be useful as diagnostic biomarkers for some psychiatric disorders.

Alzheimer's disease (AD) is the most prevalent type of dementia. Despite considerable advances in diagnostic accuracy, diagnostic procedures that are easily accessible are still sorely needed. Blood biomarkers are therefore in the focus of research. Platelets contain a high concentration of the amyloid precursor protein (APP), which has been mentioned as a potentially useful diagnostic marker. The aim of the present study was to analyze various cell adhesion molecules (CAMs), cytokines, growth factors, and matrix metalloproteinases (MMPs) in platelets of AD and mild cognitively impaired (MCI) patients as compared to healthy controls. Our data show a significant decrease in the levels of epidermal growth factor (EGF) and of MMP-2 in platelets of AD patients and decreased levels of MMP-2 in MCI. The APP ratio was slightly but not significantly decreased in AD patients, whereas CD40L and serotonin were unchanged. Our findings demonstrate specific changes in AD platelets. Whether these biomarkers can be established as potential early diagnostic biomarkers for AD remains to be established in longitudinal studies.

Alzheimer’s disease (AD) is characterized by extracellular beta-amyloid plaques and intracellular tau tangles. AD-related pathology is often accompanied by vascular changes. The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis. Platelets circulate along the vessel wall responding immediately to vascular injury. The aim of the present study was to explore the presence and migration of platelets (thrombocytes) to sites of small vascular bleedings and/or to beta-amyloid plaques in the brain. We infused fluorescently labeled red PKH26 mouse platelets into transgenic Alzheimer mice overexpressing APP with Swedish/Dutch/Iowa mutations (APP_SDI) and explored if platelets migrate into the brain. Further we studied whether platelets accumulate in the vicinity of β-amyloid plaques. Our animal data shows that infused platelets are found in the liver and partly in the lung, while in the brain platelets were visible to a minor degree. In mice, we did not observe a significant association of platelets with beta-amyloid plaques or vessels. In the brain of Alzheimer postmortem patients platelets could be detected by immunohistochemistry for CD41 and CD62P, but the majority was found in vessels with or without beta-amyloid load, and only a few single platelets migrated deeper into the brain. Our findings suggest that platelets do not migrate into the brains of Alzheimer disease but are concentrated in brain vessels.