**1. Introduction**

Alzheimer's disease (AD) is a progressive, devastating, irreversible neurodegenerative disorder of the central nervous system, which has been recognized as the most common cause of serious cognitive decline in elderly people, resulting in profound dementia [1, 2] with no effective therapeutic intervention [3]. It is reasonable that AD induces a huge social burden and has a serious economic impact, since it starts frequently as mild cognitive impairment, resulting eventually in dementia, as the time advances [4, 5], affecting over 26 million people worldwide [6, 7].

cells, astrocytes, and endothelial cells in various brain structures, including the cerebellum [40, 41], which are associated with tremendous spinal loss and loss of dendritic branches. It is important that morphological changes of the Golgi complex [42] have been observed in early cases of AD, in areas of the brain with minimal Alzheimer's pathology, suggesting that the protein trafficking might be impaired from the initial stages of AD, since Golgi apparatus plays a crucial role in trafficking and targeting of the plasma membrane proteins [43, 44].

The Hypothalamus in Alzheimer's Disease http://dx.doi.org/10.5772/intechopen.81475 77

Autonomic disorders have frequently been observed in patients who suffer from AD.Particularly, autonomic failure frequently occurs under strong emotional or cognitive stimuli during the disease, since the hypothalamus may be seriously involved even in the early stages of the neurodegenerative diseases, including AD [45–49], whereas the suprachiasmatic nucleus (SCN), the main circadian pacemaker, undergoes several continuous alterations during the course of

Stress, which is presumably a potential risk factor, mediated via the hypothalamic-pituitaryadrenal (HPA) pathway, may induce a substantial increase of glucocorticoids [49, 50], affect-

An evidence of the involvement of the hypothalamus in cases of AD is the increased volume of the third ventricle, seen in neuroimaging. In addition, there are substantial molecular and cellular differences in the morphological elements in the hypothalamus in cases of AD [51, 52], in correlation with the hippocampus and the involved cortical structures [53]. In addition, they do not contain tau-, neurofilament-, or microtubule-associated protein-reactive epitopes, and do not disrupt the neuropil or induce gliosis [53]. Numerous diffuse neuritic plaques in the hypothalamus in cases of AD are labeled with an antiserum to the Aβ peptide, of the beta-amyloid precursor proteins (beta APPs), whereas Aβ peptide-immunoreactive plaques were uncommon in the hypothalamus of non-AD patients [54]. It was also noticed that the neurofibrillary degeneration in the hypothalamus involves primarily those neurons, which are associated with

We proceeded in studying the morphological changes of the neurons and the neuronal networks of the hypothalamus in early cases of Alzheimer's disease, focusing our observations mainly on the suprachiasmatic (SCN), the supraoptic (SON), and the paraventricular nuclei

We described the alterations of dendrites, spines, and dendritic arbors in specimens impregnated by silver nitrate, using light microscope, whereas the mitochondrial alterations as well as the morphological and morphometric changes of Golgi apparatus have been studied and

Our morphological observations are based on the study of 14 brains of patients, aged 54–82 years, who suffered from AD. The brains were excised at autopsy, performed between

ing seriously the homoeostatic equilibrium of the patients.

cortical areas seriously affected by Alzheimer's pathology [55].

the disease [50].

(PVN) of the hypothalamus.

described in electron microscopy.

**2. Material and methods**

**2.1. Material**

The pathogenesis of AD involves a considerable number of cellular and molecular underlying mechanisms, as well as many genetic or acquired overlapping risk factors [8], such as diabetes, obesity, and psychosocial stress, which although are among the modifiable factors, may contribute substantially in the rapid mental deterioration, aggravating the clinical phenomenology of the disease [9].

A substantial number of clinical observations and laboratory investigations plead in favor of brain injury [8], stress [10–12], or stress-related psychiatric disorders [13, 14], type 2 diabetes [15, 16], insulin resistance [17, 18], inflammation [19] and depression [20] which may be considered, as probable predisposing factors for AD [21].

The neuropathological findings in AD are numerous. Among them, the amyloid containing neuritic plaques, the neurofibrillary tangles, which consist of intraneuronal aggregation of highly phosphorylated tau proteins, the morphological alterations of dendrites and spines, the synaptic pathology, and the increased neuronal loss in limbic structures and the cortex of the brain hemispheres are considered as hallmarks of the disease [22–24]. The gradual accumulation of Aβ peptide in the brain may induce inflammatory reactions, in which activated microglial cells are mostly involved [24]. It is important that the aggregation of Aβ amyloid peptide may promote selective degeneration of neurons, which are particularly vulnerable to age-related procedures, to oxidative stress, and any other type of energy deficiency [25]. The disruption of the blood brain barrier and the pathology of capillaries play a substantial role in shaping the neuropathological pattern of AD [26, 27], since they can facilitate the infiltration of immune cells promoting the exacerbation of inflammatory reactions in the brain.

The initial clinical manifestations of AD are subtle. However, as the time advances, progressive memory and learning impairment [28]; language disturbances; visuospatial disorientation; ideomotor apraxia; behavioral disturbances; depressive symptoms [29–32]; personality changes [33–35]; and a multitude of non-cognitive symptoms, such as sleep disruption, circadian dysrhythmia, changes in body weight, and autonomic dysfunction, are progressively established as dominant deficits in AD [36]. Sleep disturbances, on the other hand, might have a negative impact on the amyloid burden and the cognitive capacity of the patients, though the entire pathogenetic mechanism in sporadic cases remains unclear and is only approached by various hypotheses. The study of familial cases of AD, on the other hand, advocates in favor of the heterogeneity of the disease, and suggests that the morphological alterations in AD follow an eventual common pathway with many other degenerative conditions of the CNS [37, 38].

Oxidative stress seems to contribute substantially in the pathogenesis of AD [39, 40]. In addition, electron microscopy revealed serious morphological alterations of mitochondria in nerve cells, astrocytes, and endothelial cells in various brain structures, including the cerebellum [40, 41], which are associated with tremendous spinal loss and loss of dendritic branches. It is important that morphological changes of the Golgi complex [42] have been observed in early cases of AD, in areas of the brain with minimal Alzheimer's pathology, suggesting that the protein trafficking might be impaired from the initial stages of AD, since Golgi apparatus plays a crucial role in trafficking and targeting of the plasma membrane proteins [43, 44].

Autonomic disorders have frequently been observed in patients who suffer from AD.Particularly, autonomic failure frequently occurs under strong emotional or cognitive stimuli during the disease, since the hypothalamus may be seriously involved even in the early stages of the neurodegenerative diseases, including AD [45–49], whereas the suprachiasmatic nucleus (SCN), the main circadian pacemaker, undergoes several continuous alterations during the course of the disease [50].

Stress, which is presumably a potential risk factor, mediated via the hypothalamic-pituitaryadrenal (HPA) pathway, may induce a substantial increase of glucocorticoids [49, 50], affecting seriously the homoeostatic equilibrium of the patients.

An evidence of the involvement of the hypothalamus in cases of AD is the increased volume of the third ventricle, seen in neuroimaging. In addition, there are substantial molecular and cellular differences in the morphological elements in the hypothalamus in cases of AD [51, 52], in correlation with the hippocampus and the involved cortical structures [53]. In addition, they do not contain tau-, neurofilament-, or microtubule-associated protein-reactive epitopes, and do not disrupt the neuropil or induce gliosis [53]. Numerous diffuse neuritic plaques in the hypothalamus in cases of AD are labeled with an antiserum to the Aβ peptide, of the beta-amyloid precursor proteins (beta APPs), whereas Aβ peptide-immunoreactive plaques were uncommon in the hypothalamus of non-AD patients [54]. It was also noticed that the neurofibrillary degeneration in the hypothalamus involves primarily those neurons, which are associated with cortical areas seriously affected by Alzheimer's pathology [55].

We proceeded in studying the morphological changes of the neurons and the neuronal networks of the hypothalamus in early cases of Alzheimer's disease, focusing our observations mainly on the suprachiasmatic (SCN), the supraoptic (SON), and the paraventricular nuclei (PVN) of the hypothalamus.

We described the alterations of dendrites, spines, and dendritic arbors in specimens impregnated by silver nitrate, using light microscope, whereas the mitochondrial alterations as well as the morphological and morphometric changes of Golgi apparatus have been studied and described in electron microscopy.
