**Author details**

574 Lipoproteins – Role in Health and Diseases

several neuropathologies.

**5. Conclusion** 

Overall, these data emphasizes the relevance of plasma lipoprotein metabolism in brain physiology and the convergence of similar dysfunctions of this metabolism associated with

This review has addressed MS and AD as a strategy to explore the potential relevance of plasma lipoproteins in CNS inflammatory and neurodegenerative disorders. Despite quite different in their demographics, clinical and pathological characteristics, some similarities in their inflammatory and neurodegenerative components have been noted previously [102].

In MS as in AD, the genesis of brain pathology is thought to begin many years before the clinical overt disease. Despite the occurrence of widespread lesions, brain plastic compensatory mechanisms may maintain those disorders clinically silent, delay their symptoms or modify their clinical evolution. Molecular mechanisms underlying grey and white matter plasticity are of outstanding neurobiological and medical importance and are currently poorly understood [111]. This review suggests that an involvement of lipoprotein metabolism in brain plasticity

Clinical signs of MS very rarely first appear in individuals after 60 years of age and sporadic AD rarely manifest before that age. However, it is remarkable that a profile of low HDLcholesterol, apoE and apoA-I plasma levels and elevated total and non-HDL cholesterol may promote the risk or progression of disability in both disorders. As discussed, this profile could be associated with both the genesis of lesions in the CNS and the systemic immunerelated or metabolic alterations implicated in their pathophysiology (Table 1, Figure 1). It is to note that disturbances in brain cholesterol transport (that may occur in MS, AD and other neuropathologies) can lead to alterations in cholesterol uptake from plasma to brain and decrease plasma HDL levels (112). In MS as in AD, this lipoprotein profile may promote foam cell plaque formations. In young individuals genetically susceptible to MS, this profile may promote the genesis of demyelinating plaques; instead with advanced age, atheroma plaques formation prevails, contributing to AD, in genetically susceptible subjects. Supporting this speculation, MS pathogenesis may share many lipoprotein-related and inflammatory mechanisms underlying atherogenesis (Table1). In addition, with aging, this lipoprotein profile could have a convergent impact for the maintenance of the typical CNS lesions occurring in MS and AD. In fact, advanced ageing may be associated with lower recruitment of anti-inflammatory and phagocytic macrophages and other blood-derived factors to the CNS [113]. This situation, on one hand, favors lower capacity of β-amyloid clearance, oligodendrocyte toxicity and myelin lesions, early present in incipient AD. On the other hand, it restricts remyelination capacities in MS, which are more accentuated with advancing ageing in these patients. The presence of age-related changes in blood circulation has recently been noted of possible relevance for MS and AD [114]. These relevant age-

mechanisms is highly plausible and deserves much future research.

related changes should comprise circulating lipoprotein metabolism.

Despite the similarities of lipoproteins involvement in these two disorders, including the neuroprotective, immunosuppressive and vascular/ischemic protective functions of HDL-

Armando Sena, Carlos Capela, Camila Nóbrega and Elisa Campos *Centro de Estudos de Doenças Crónicas (CEDOC), Faculdade de Ciências Médicas, UNL, Campo Mártires da Pátria, Lisboa, Portugal* 

Armando Sena, Carlos Capela, Camila Nóbrega and Rui Pedrosa *Serviço de Neurologia, Hospital dos Capuchos, Centro Hospitalar de Lisboa-Central, Lisboa, Portugal* 

Armando Sena, Camila Nóbrega and Véronique Férret-Sena *Interdisciplinary Centre of Research Egas Moniz (CRiEM), Cooperativa Egas Moniz, Monte da Caparica, Portugal* 

#### **Acknowledgement**

The authors thank to nurses Cristina Araújo and Ana Mendes (Neurology Service) for helping in research and dedicated assistance to our patients and to Merck-Serono, Biogen Idec, Bayer HealthCare, Lundbeck, Octapharma, Teva Pharma and Sanofi-Aventis for supporting our research.

#### **6. References**


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576 Lipoproteins – Role in Health and Diseases

The authors thank to nurses Cristina Araújo and Ana Mendes (Neurology Service) for helping in research and dedicated assistance to our patients and to Merck-Serono, Biogen Idec, Bayer HealthCare, Lundbeck, Octapharma, Teva Pharma and Sanofi-Aventis for

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**Chapter 24** 
