**Author details**

proteotoxicity [99, 100]. In addition, impaired mitochondrial biogenesis contributes to mitochondrial dysfunction [101], which is directly associated with the oxidative stress, the main

Mitochondrial motility and accumulation are related to the functional state of the neuron, since mitochondria are transported to regions where necessity for energy is particularly high, as it occurs in the dendritic and axonal profiles and the synapses [103–105]. The shape and size of mitochondria are not stable, since they undergo continual fission and fusion which are necessary for cell survival and harmonious adaptation to changing conditions. Recent studies reported increased mitochondrial fission and decreased fusion, due to increased Aβ peptide interaction with the mitochondrial fission protein Drp 1, inducing increased mitochondrial fragmentation, impaired axonal transport of mitochondria and synaptic degeneration in AD [106, 107]. The consequence of the dynamic fusion and fission processes is the eventual

Nevertheless, a considerable diminution of the mitochondria is also seen in aging-related neurodegeneration [97, 98], as well as in the early stages of AD, when the mental decline is subtly detected [107]. In normal brains, few spines only contain small round mitochondria in contrast to dendritic branches which mostly include large mitochondria that become numerous during synaptogenesis and in various conditions of hormonal disequilibrium [104, 106]. In AD, marked morphological changes of the mitochondria have been observed in neurons, which show an extensive loss of dendritic spines, associated with giant spines, distortion of spines and synaptic loss. The association of mitochondrial pathology with the synaptic loss is reasonably attributed to a sharp decrease of energy supply by the defected mitochondria [106, 108], a fact which occurs even at the initial stages of AD, when the typical Alzheimer pathology, consisted of the neuritic plaques and the neurofibrillary tangles is

The mitochondrial pathology, which is observed in the neurons of the hypothalamic nuclei are additional evidences of the causative role that mitochondrial dysfunction play in synaptic degeneration and loss of dendritic arbores in AD [111, 112]. In the suprachiasmatic nucleus of the hypothalamus a substantial number of neurons made evident the marked decrease of the spine density at the secondary and tertiary dendritic branches, which affects reasonably the neuronal interactions in AD. A substantial body of evidence plead also in favor of the important role that mitochondria and Golgi complex play in the morphological and the quantitative stability of the dendritic spines in neuronal networks [105, 109–112], whereas experimental

The hypothalamus play a central role in autonomic functions, including the generation and control of the circadian rhythms, the thermoregulation, the homeostasis of proteins [25], the maintenance of energy supply and the feeding behavior [113–115]. The pathological alterations of hypothalamic nuclei in AD would induce the autonomic instability, which would be particularly prominent at the advanced stages of the disease, aggravating the clinical condition of the patients exceedingly [116–118], a fact which is also observed in experimental mod-

els of AD [119] as well as in the behavioral variant of frontotemporal dementia [120].

studies underline the spinal vulnerability to nonfibrillar Aβ peptide [110].

activator of the pathogenic cascade of AD [101–103].

mitophagy of the damaged mitochondria.

still minimal [109, 110].

180 Cognitive Disorders

Stavros Ioannou Baloyannis1,2\*, Ioannis Mavroudis1 , Demetrios Mitilineos1 , Ioannis S. Baloyannis1 and Vasiliki G. Costa1,2

\*Address all correspondence to: sibh844@otenet.gr

1 1st Department of Neurology, Laboratory of Neuropathology and Electron Microscopy, Aristotelian University of Thessaloniki, Thessaloniki, Greece

2 Institute for Research on Alzheimer's disease, Iraklion, Lagada, Greece
