[Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II)]. / ¿Existe la enfermedad de Alzheimer en todos los primates? Patología Alzheimer en primates no humanos y sus implicaciones fisiopatológicas (II).

INTRODUCTION: In the ageing process there are some species of non-human primates which can show some of the defining characteristics of the Alzheimer's disease (AD) of man, both in neuropathological changes and cognitive-behavioural symptoms. The study of these species is of prime importance to understand AD and develop therapies to combat this neurodegenerative disease. DEVELOPMENT: In this second part of the study, these AD features are discussed in the most important non-experimental AD models (Mouse Lemur -Microcebus murinus, Caribbean vervet -Chlorocebus aethiops, and the Rhesus and stump-tailed macaque -Macaca mulatta and M. arctoides) and experimental models (lesional, neurotoxic, pharmacological, immunological, etc.) non-human primates. In all these models cerebral amyloid neuropathology can occur in senility, although with different levels of incidence (100% in vervets;<30% in macaques). The differences between normal and pathological (Alzheimer's) senility in these species are difficult to establish due to the lack of cognitive-behavioural studies in the many groups analysed, as well as the controversy in the results of these studies when they were carried out. However, in some macaques, a correlation between a high degree of functional brain impairment and a large number of neuropathological changes ("possible AD") has been found. CONCLUSIONS: In some non-human primates, such as the macaque, the existence of a possible continuum between "normal" ageing process, "normal" ageing with no deep neuropathological and cognitive-behavioural changes, and "pathological ageing" (or "Alzheimer type ageing"), may be considered. In other cases, such as the Caribbean vervet, neuropathological changes are constant and quite marked, but its impact on cognition and behaviour does not seem to be very important. This does assume the possible existence in the human senile physiological regression of a stable phase without dementia even if neuropathological changes appeared.

[Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (I)]. / ¿Existe la enfermedad de Alzheimer en todos los primates? Afección de Alzheimer en primates no humanos y sus implicaciones fisiopatológicas (I).

INTRODUCTION: Many publications consider that Alzheimer's disease (AD) is exclusive to the human species, and that no other animal species suffers from the disease. However, various studies have shown that some species can present with some of the defining characteristics of the human disease, including both neuropathological changes and cognitive-behavioural symptoms. DEVELOPMENT: In this work, the results published (PubMed) on senile brain changes in non-human primates of different degrees of evolution, are reviewed. The neuropathological changes associated with the accumulation of amyloid or highly phosphorylated tau protein are rare outside the primate order, but in all the sub-orders, families, genera and species of non-human primates that have been studied, some senile individuals have shown amyloid accumulation in the brain. In fact, in some species the presence of these deposits in senility is constant. Changes related to the accumulation of tau protein are always of very little significance, and have been detected only in some non-human primate species, both little evolved and highly evolved. In different species of non-human primates, some types of cognitive-behavioural changes are more common in some senile individuals when compared with both normal adult individuals and other senile individuals of the species. The importance of determining the longevity of the species in different habitats (natural habitats, new habitats, semi-captivity, captivity) is stressed in these studies. CONCLUSIONS: Morphological, histochemical and cognitive-behavioural features similar to those observed in elderly humans are present in senile non-human primates. Moreover, other characteristics seen in non-human primates could be indicative of a pathological «Alzheimer type¼ ageing.

[Neurogenesis as a therapeutic target for Alzheimer's disease]. / Neurogénesis como diana terapéutica para la enfermedad de Alzheimer.

INTRODUCTION: The adult brain of mammals preserves the capacity to generate new neurons from neural stem/progenitor cells. The new neurons become part of the already-existing networks by means of a process called 'neurogenesis in the adult brain', which is restricted to regions of the brain with a high degree of plasticity and which are associated to functions that are impaired in Alzheimer's disease. DEVELOPMENT: Despite increasing knowledge, there are still many questions surrounding these neurogenic phenomena, their regulation and their real therapeutic potential in cases of neurodegeneration such as the one referred to here. CONCLUSIONS: We have reviewed the subject of neurogenesis of the adult brain from both the pre-clinical point of view (experimental modelling) and the therapeutic perspective within the framework of Alzheimer's disease.

Effects of nerve growth factor on brain glutathione-related enzymes from aged rats.

Neurotrophins, like the nerve growth factor (NGF), trigger a variety of biological effects in their targets. Stimulating effects on antioxidant defenses have been postulated to underlie neurotrophic influence on neuron survival and maintenance. To test whether NGF is capable of inducing changes in glutathione-related enzymes in the aged cognitively impaired brain, glutathione reductase (GRD), glutathione S-transferase (GST) and total glutathione peroxidase (GPX) activities were measured in the striatum, septum, hippocampus and frontal cortex of four Sprague-Dawley rat groups: young (2 months old), aged (20 months old) untreated, aged cytochrome c-treated, and aged NGF-treated (icv delivery, 34 micrograms during 28 days). All the aged rats utilized in the study were memory impaired according to their performance in the Morris water maze test. These aged rats showed increases in the activities of septal and hippocampal GST, as well as, in the hippocampal, striatal and cortical GPX. These increases could be interpreted as compensatory responses to cope with the oxidative damage that has been accumulated by the aged brain. The increases in hippocampal and cortical GPX activity were attenuated by NGF treatment, whereas the neurotrophin induced an increase in GRD activity in the striatum of aged rats. These results point out GRD and GPX as possible targets of the neurotrophic effects.