Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY3-36 (PYY3-36), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY3-36 in rats inhibits food intake and reduces weight gain. PYY3-36 also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY3-36 increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY3-36 inhibits food intake. PYY3-36 also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY3-36 significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut–hypothalamic pathway.

BRIEF COMMUNICATION ARISING: Gut hormone PYY3-36 physiologically inhibits food intake

Alzheimer's disease (AD) is classically defined as a dual clinicopathological entity. The recent advances in use of reliable biomarkers of AD that provide in-vivo evidence of the disease has stimulated the development of new research criteria that reconceptualise the diagnosis around both a specific pattern of cognitive changes and structural/biological evidence of Alzheimer's pathology. This new diagnostic framework has stimulated debate about the definition of AD and related conditions. The potential for drugs to intercede in the pathogenic cascade of the disease adds some urgency to this debate. This paper by the International Working Group for New Research Criteria for the Diagnosis of AD aims to advance the scientific discussion by providing broader diagnostic coverage of the AD clinical spectrum and by proposing a common lexicon as a point of reference for the clinical and research communities. The cornerstone of this lexicon is to consider AD solely as a clinical and symptomatic entity that encompasses both predementia and dementia phases.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(10)70223-4.pdf

Revising the definition of Alzheimer's disease: a new lexicon.

Defeating Alzheimer's disease and other dementias : a priority for European science and society

/pdf/defeating-alzheimer-s-disease-and-other-dementias-a-priority-2d414i7vsl.pdf

Defeating Alzheimer's disease and other dementias: a priority for European science and society

https://sites.oxy.edu/clint/physio/article/Memoryagingandbrainmaintenance.pdf

Memory aging and brain maintenance

http://pr.korea.ac.kr/bbs/download.php?bo_table=sub4_1&wr_id=101&no=0

Hierarchical feature representation and multimodal fusion with deep learning for AD/MCI diagnosis.

In Alzheimer disease (AD), which is the most common cause of dementia, the underlying disease pathology most probably precedes the onset of cognitive symptoms by many years. Thus, efforts are underway to find early diagnostic markers as well as disease-modifying treatments for this disorder. PET enables various brain systems to be monitored in living individuals. In patients with AD, PET can be used to investigate changes in cerebral glucose metabolism, various neurotransmitter systems, neuroinflammation, and the protein aggregates that are characteristic of the disease, notably the amyloid deposits. These investigations are helping to further our understanding of the complex pathophysiological mechanisms that underlie AD, as well as aiding the early and differential diagnosis of the disease in the clinic. In the future, PET studies will also be useful for identifying new therapeutic targets and monitoring treatment outcomes. Amyloid imaging could be useful as early diagnostic marker of AD and for selecting patients for anti-amyloid-beta therapy, while cerebral glucose metabolism could be a suitable PET marker for monitoring disease progression. For the near future, multitracer PET studies are unlikely to be used routinely in the clinic for AD, being both burdensome and expensive; however, such studies are very informative in a research context.

The use of PET in Alzheimer disease

Learning and forgetting new names and objects in MCI and AD.

Alzheimer’s disease (AD) is a common degenerative neurological disease that is an increasing medical, economical, and social problem. There is evidence that a long “asymptomatic” phase of the disease exists where functional changes in the brain are present, but structural imaging for instance with magnetic resonance imaging remains normal. Positron emission tomography (PET) is one of the tools by which it is possible to explore changes in cerebral blood flow and metabolism and the functioning of different neurotransmitter systems. More recently, investigation of protein aggregations such as amyloid deposits or neurofibrillary tangles containing tau-protein has become possible. The purpose of this paper is to review the current knowledge on various 18F- and 11C-labelled PET tracers that could be used to study the pathophysiology of AD, to be used in the early or differential diagnosis or to be used in development of treatment and in monitoring of treatment effects.

Radiopharmaceuticals for positron emission tomography investigations of Alzheimer’s disease

Signaling through the leukemia inhibitory factor (LIF) receptor (LIFR) is crucial for nervous system development. There are few studies concerning the expression of LIF and LIFR in normal and degenerating adult human brain. Objectives - To study the expression of LIF and LIFR in Alzheimers disease (AD), Parkinsonsd isease (PD), and control brains. Patients and methods - LIF and LIFR mRNA copy numbers were determined by quantitative real-time RT-PCR from four brain regions of 34 patients with AD, 40 patients with PD, and 40 controls. Immunohistochemistry was performed in seven PD and in four AD patients and in seven normal controls. Results - In general, the LIF copy numbers were 1 log higher than the LIFR copy numbers. In the AD brains, LIF expression was higher than in the controls in the hippocampus and in the temporal cortex, and in the PD brains in the hippocampus and in the anterior cingulated cortex. Expressions of LIF and LIFR in different brain regions were opposite except for the AD hippocampus and PD anterior cingulated cortex, where the expression patterns were parallel. Conclusions - Co-operative expression of LIF and LIFR in AD hippocampus and PD anterior cingulated cortex may indicate a role for LIF in neuronal damage or repair in these sites.

Expression of LIF and LIF receptor beta in Alzheimer's and Parkinson's diseases.

Mild cognitive impairment (MCI) is considered a transitional state between the cognitive changes of normal aging and the earliest clinical features of Alzheimer's disease (AD). An important goal is to find features that predict which MCI patients will later convert to AD. Identification of such features will be increasingly important when treatments slowing down the progression of AD become available enabling early intervention. Brain imaging might be one possible predictor of conversion to AD. Functional imaging with positron emission tomography (PET) has shown that either normal elderly people carrying apolipoprotein E epsilon4 allele or people with MCI already show reduced cerebral glucose metabolism in those brain areas that are typically affected in AD. Investigations of different neurotransmitter systems might increase specificity and help in the differential diagnosis between dementing disorders. Dopamine transporter imaging to aid in the differential diagnosis between AD and dementia with Lewy bodies seems promising. Amyloid imaging is an example of "pathology specific" imaging that has great potential to enhance early detection of AD processes and to help in differential diagnosis. In the future, multi-tracer imaging or development of agents enabling imaging of other protein aggregations in neurodegenerative diseases could further help in the early and differential diagnostics and evaluation of novel treatments.

Juha O. Rinne

Papers

The use of PET in Alzheimer disease

Learning and forgetting new names and objects in MCI and AD.

Radiopharmaceuticals for positron emission tomography investigations of Alzheimer’s disease

Expression of LIF and LIF receptor beta in Alzheimer's and Parkinson's diseases.

Positron Emission Tomography in at Risk Patients and in the Progression of Mild Cognitive Impairment to Alzheimer's Disease