Olfactory dysfunction is a frequent and early feature of patients with neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) and is very uncommon in patients with frontotemporal dementia (FTD). Mechanisms underlying this clinical manifestation are poorly understood but the premature deposition of protein aggregates in the olfactory bulb (OB) of these patients might impair its synaptic organization, thus accounting for the smell deficits. Tau, β-amyloid and alpha-synuclein deposits were studied in 41 human OBs with histological diagnosis of AD (n = 24), PD (n = 6), FTD (n = 11) and compared with the OB of 15 control subjects. Tau pathology was present in the OB of all patients, irrespective of the histological diagnosis, while β-amyloid and alpha-synuclein protein deposit were frequently observed in AD and PD, respectively. Using stereological techniques we found an increased number of dopaminergic periglomerular neurons in the OB of AD, PD and FTD patients when compared with age-matched controls. Moreover, volumetric measurements of OBs showed a significant decrease only in AD patients, while the OB volume was similar to control in PD or FTD cases. The increased dopaminergic tone created in the OBs of these patients could reflect a compensatory mechanism created by the early degeneration of other neurotransmitter systems and might contribute to the olfactory dysfunction exhibited by patients with neurodegenerative disorders.

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Background: Learning processes or language development are only some of the cognitive functions that differ qualitatively between men and women. Gender differences in the brain structure seem to be behind these variations. Indeed, this sexual dimorphism at neuroanatomical level is accompanied unequivocally by differences in the way that aging and neurodegenerative diseases affect men and women brains.Objective: The aim of this study is the analysis of neuronal density in four areas of the hippocampus, and entorhinal and frontal cortices to analyze the possible gender influence during normal aging and in Alzheimer's disease (AD).Methods: Human brain tissues of different age and from both sexes, without neurological pathology and with different Braak's stages of AD, were studied. Neuronal density was quantified using the optical dissector.Results: Our results showed the absence of a significant neuronal loss during aging in non-pathological brains in both sexes. However, we have demonstrated specific punctual significant variations in neuronal density related with the age and gender in some regions of these brains. In fact, we observed a higher neuronal density in CA3 and CA4 hippocampal areas of non-pathological brains of young men compared to women. During AD, we observed a negative correlation between Braak's stages and neuronal density in hippocampus, specifically in CA1 for women and CA3 for men, and in frontal cortex for both, men and women.Conclusion: Our data demonstrated a sexual dimorphism in the neuronal vulnerability to degeneration suggesting the need to consider the gender of the individuals in future studies, regarding neuronal loss in aging and AD, in order to avoid problems in interpreting data.

Apolipoprotein D (apo D) is a lipocalin present in the nervous system that may be related to processes of reinnervation, regeneration and neuronal cell protection. On the other hand, apo D expression has been correlated, in some brain regions, with normal ageing and neurodegenerative diseases. To elucidate the regional and cellular expression of apo Din normal human brain during ageing, we performed a detailed and extensive study in samples of post-mortem human cerebral cortices. To achieve this study, slot-blot techniques, for protein and mRNA,as well as immunohistochemistry and hybridohistochemistry methods, were used. A positive correlation for apo D expression with ageing was found;furthermore, mRNA levels, as well as the protein ones, were higher in the white than in the grey matter. Immunohistochemistry and non-isotopic in situ hybridization showed that apo D is synthesised in both neurons and glial cells. Apo D expression is notorious in oligodendrocytes, but with ageing, the number of neurons that synthesise apo D is increased.Our results indicate that apo D could play a fundamental role in central nervous system ageing and in the reduction of products derived from lipid peroxidation. The increment in the expression of apo D with ageing can be included in a global mechanism of cellular protection to prevent the deleterious effects caused by ageing.

Apolipoprotein D (Apo D) is a lipid binding protein whose expression is strongly induced in the mammalian brain during aging and age-dependent neurodegenerative diseases such as Alzheimer's disease (AD), where it can play an important function as a neuroprotective and antioxidant protein. Increasing evidence suggests that the gradual increase in free radicals and oxidative stress with age is the primary determinant to aging brain. The aim of this work is to study the effect of hydrogen peroxide (H2O2) in Apo D expression, in hippocampal cells, in order to investigate the relationship between oxidative stress and elevated levels of Apo D found in hippocampus during aging and AD and also elucidate the possible pathways that lead to this increase. In this study, we demonstrated that Apo D expression in hippocampal neurons of aged and AD brains directly correlates with age-related increase in oxidative stress. More importantly, our results in the HT22 cell line indicate that Apo D protein level increases in a concentration-dependent manner specifically at those H2O2 concentrations that caused oxidative damage and apoptotic cell death. These data support the idea that oxidative stress-induced apoptosis during aging and AD may be associated with the increment in the expression of Apo D in these situations.