**Conflict of interest**

synaptic degeneration in AD [99]. The consequence of the dynamic fusion and fission pro-

A prominent decrease of the size of the mitochondria is observed in aging-related neurodegenerative diseases [95, 96], as well as at the early stages of AD, prior to the onset of a noticeable cognitive dysfunction [105]. Normally, a limited number of dendritic spines contain small and round mitochondria, which are increased in number in the dendritic profiles during the synaptogenesis and hormonal instability [102, 104]. It is important to underline that mitochondrial alterations are mostly associated with synaptic loss in AD patients, due to impairment of mitochondrial energy production [106], seen even before the typical genera-

The morphological alteration of the mitochondria, seen in the hypothalamic nuclei in early cases of Alzheimer's disease, pleads in favor of a generalized mitochondrial dysfunction in AD, which may be associated with the dendritic pathology, the tremendous loss of spines,

The density of the spines on the dendritic branches of a considerable number of neurons of the suprachiasmatic nucleus was decreased. The loss of the dendritic spines causes substantial impairment in neuronal communication and also induces reasonable dysfunction of the neuronal circuits in AD. Previous observations revealed that the loss of dendritic spines coincides with the morphological alterations of the mitochondria and the fragmentation of the cisternae of Golgi apparatus [25, 102, 109, 110]. In an experimental mouse model of Aβ peptide deposition, it was revealed that nonfibrillar Aβ peptide may exert toxicity on the spines, resulting in

The role of the hypothalamus in the harmonization of circadian rhythms is crucial for the maintenance of energy homeostasis [25]. The feeding behavior [111–113] and the thermoregulation of the body become gradually unstable during the clinical course of AD [114–116], a fact which was also noticed in experimental models of AD [117] as well as in the behavioral

In conclusion, the hypothalamic nuclei are involved in AD, inducing autonomic dysfunction and homeostatic disequilibrium, phenomena which are clearly noticeable at the advanced

In Alzheimer's disease, silver impregnation technique and electron microscopy revealed a substantial decrease of the neuronal population, which is particularly obvious in the supra-

The silver staining technique demonstrated a marked shortage of the dendritic arborization of

It must be underlined that Alzheimer's pathology, such as neuritic plaques and neurofibrillary degeneration, is minimal in hypothalamus in comparison with other areas of the brain.

cesses is the eventual mitophagy of the damaged mitochondria.

tion of the neuritic plaques and tau pathology [105, 107].

and the marked synaptic alterations [108–110].

88 Hypothalamus in Health and Diseases

dramatic decrease of spine density [108, 111].

variant of fronto-temporal dementia [118].

chiasmatic nucleus of the hypothalamus.

neurons, associated with spinal pathology and axonal dystrophy.

stages of AD.

**5. Conclusions**

No conflict of interest.
