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Keywords
Alzheimer’s disease, Hypothalamus, Organelles, Electron microscopy, Morphometry, Aβ peptide, Synaptic plasticity
Abbreviations
AD, Alzheimer’s Disease; GA, Golgi Apparatus; ER, Endoplasmic Reticulum; SCN, Suprachiasmatic Nucleus; PVN, Paraventricular Nucleus; SST, somatostatin; CRs, Circadian Rhythms
Editorial
Alzheimer’s disease (AD) is a progressive devastating neurodegenerative disease causing serious irreversible cognitive decline in presenile and senile age, having considerable social, legal, ethical1 and economic impact.2 The clinical phenomena of the disease include prominent memory and learning impairment, attention deficit, gradual deterioration of judgment,executive dysfunction,language disturbances, visuospatial disorientation, which sometimes is obvious even at the initial stages of the disease, behavioral and mood disturbances associated with personality alterations and progressively autonomic dysfunction, changes in the endocrine system and physical decline, which become particularly prominent as the disease advances.3
The neuropathological alterations include neurofibrillary tangles consisting of highly phosphorylated tau proteins, extracellular aggregates of Aβ peptide in the form of neuritic plaques, dendritic alterations, synaptic loss, selective neuronal loss4 affecting mostly the limbic and neocortical areas and blood–brain barrier disruption and microvascular lesions, which contribute also in plotting the neuropathological profile of AD.5
Electron microscopy enlarges the horizons of morphological alterations in AD visualizing clearly the substantial synaptic loss in association with marked alterations of the organelle involving mostly mitochondria,6 Golgi apparatus (GA),7,8 and endoplasmic reticulum (ER)9 clearly observed even in areas of the brain, where dendritic plaques and neurofibrillary tangles are infrequent.
Autonomic dysfunction has been frequently reported in ADeither as hyperactivity or as failure of the autonomic system.10 The autonomic responses to emotional or cognitive stimuli may be impaired, even in the initial stages of AD. Hypothalamic nuclei may be implicated in AD,11 although all of them are not involved simultaneously and in the same extend. Microinflammation of the hypothalamus on the other hand may occur in aging and age related diseases such as AD.12 In the field of clinical investigation was noticed that substance P and hypocretin (orexin), which plays an important role in sleep-wake cycle and food intake, were elevated in the CSF in a substantial number of AD patients in comparison with normal controls.13,14 Somatostatin (SST) is consistently reduced in the hypothalamus and neocortical areas in AD,15,16 correlating with cognitive decline, although it is well documented that the SST system is also implicated in stress, anxiety and depression.17
Neuropathological studies based on silver impregnation techniques in association with the Golgi - Nissl method, revealed marked dendritic alterations. Loss of dendritic spines, abnormal spines, a considerable decrease in spine density, and substantial decrease in the neuronal population in the hypothalamic nuclei in AD, affecting primarily the suprachiasmatic nucleus (SCN). Electron microscopy revealed marked mitochondrial alterations in the soma and dendritic branches and fragmentation of Golgi apparatus in a substantial number of neurons of the SCN and PVNof the hypothalamus.18
Among the hypothalamic nuclei the SCN seems to be more seriously affected in aging19 and in a dramatic way in AD,18,20 a fact that might explain the phenomenon of desynchronization of circadian rhythms (CRs) in the majority of the patients who suffer from AD,21 since SCN is of substantial importance for the generation and the synchronization of CRs in man.22
In addition the involvement of the hypothalamic nuclei in the course of AD may explain the sleep disturbances,23 the changes of feeding behavior, energy homeostasis, and thermoregulation of the body, as well as the autonomic dysfunction, which are gradually manifested as the diseases advances and contribute in the tragic physical decline of the patients eventually.24
Acknowledgments
None.
Conflicts of interest
None.
References
- Baloyannis S. The philosophy of dementia. Encephalos. 2010;47(3):109–130.
- Stefanacci RG. The costs of Alzheimer’s disease and the value of effective therapies. Am J Manag Care. 2011;17(Suppl 13):356–362.
- Blair J A, McGee H, Bhatta S, et al. Hypothalamic–pituitary–gonadal axis involvement in learning and memory and Alzheimer’s disease: more than “just” estrogen. Front Endocrinol (Lausanne). 2015;6:45.
- Schellenberg GD, Montine TJ. The genetics and neuropathology of Alzheimer’s disease. Acta Neuropathol. 2012;124(3):305–323.
- Baloyannis SJ, Baloyannis IS. The vascular factor in Alzheimer’s disease: a study in Golgi technique and electron microscopy. J Neurol Sci. 2012;322(1–2):117–121.
- Baloyannis SJ. Alterations of mitochondria and Golgi apparatus are related to synaptic pathology in Alzheimer’s disease. In: Kishore U (Ed.), Neurodegenerative Diseases. InTech, Rijeka, Croatia. 2013;pp.101–123.
- Baloyannis S. The Golgi apparatus of Purkinje cells in Alzheimer’s disease. In: BohlJ (Ed.), Neuropathology Back to the Roots. Shaker Vertag, Aachen, Germany. 2002;p.1–10.
- Baloyannis S J. Golgi apparatus in Alzheimer’s disease. J Neurol Stroke. 2015;2(3):00056.
- Hetz C, Mollereau B. Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases. Nat Rev Neurosci. 2014;15(4):233–249.
- Idiaquez J, Roman GC. Autonomic dysfunction in neurodegenerative dementias. J Neurol Sci. 2011;305(1–2):22–27.
- Loskutova N, Honea RA, Brooks WM, et al. Reducedlimbic and hypothalamic volumes correlate with bone density in early Alzheimer’s disease. J Alzheimers Dis. 2010;20(1):313–322.
- Tang Y, Purkayastha S, Cai D. Hypothalamic microinflammation: a common basis of metabolic syndrome and aging. Trends in neurosci. 2015;38(1):36–44.
- Johansson P, Almqvist EG, WallinA, et al. Cerebrospinal fluid substance P concentrations are elevated in patients with Alzheimer's disease. Neurosci Lett. 2015;609:58–62.
- Thannickal TC. Hypocretin (orexin) pathology in Alzheimer’s disease. World J Neurol. 2015;5(3):64–67.
- Burgos–Ramos E, Hervás–Aguilar A, Aguado–Llera D, et al. Somatostatin and Alzheimer’s disease. Mol Cell Endocrinol. 2008;286(1–2):104–111.
- Ádori C, Glück L, Barde S, et al. Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system: new aspects on Alzheimer’s disease. Acta neuropath. 2015;129(4):541–563.
- Lin LC, Sibille E. Reduced brain somatostatin in mood disorders: a common pathophysiological substrate and drug target? Front Pharmacol. 2013;4:110.
- Baloyannis SJ, Mavroudis I, Mitilineos D, et al. The Hypothalamus in Alzheimer’s Disease A Golgi and Electron Microscope Study. Am J Alzheimers Dis Other Demen. 2014;30(5):478–487.
- Cai H, Cong WN, Ji S, et al. Metabolicdysfunction in Alzheimer’s disease and related neurodegenerative disorders. Curr Alzheimer Res. 2012;9(1):5–17.
- Goudsmit E, Hofman MA, Fliers E, et al. The supraoptic and paraventricular nuclei of the human hypothalamus in relation to sex, age and Alzheimer’s disease. Neurobiol Aging. 1990;11(5):529–536.
- Coogan AN, Schutová B, Husung S, et al. The circadian system in Alzheimer’s disease: disturbances, mechanisms, and opportunities. Biol Psychiatry. 2013;74(5):333–339.
- Dibner C, Schibler U, Albrecht U. The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol. 2010;72:517–549.
- Peter–Derex L, Yammine P, Bastuji H, et al. Sleep and Alzheimer's disease. Sleep med rev. 2015;19:29–38.
- Morris JK, Honea RA, Vidoni ED, et al. Is Alzheimer's disease a systemic disease? Biochim Biophys Acta. 2014;1842(9):1340–1349.
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