Aging Related Memory Disorders

Alzheimer's Disease

I. Aging-Related Memory Decline

A. Stages of AD

B. Pathological Hallmarks of AD

C. AP42 as the Cause of AD

III. Genes—Familial and Late-Onset AD

A. APP Mutations

B. Presenilin Mutations

C. ApoE4 Alleles in AD

IV. Apolipoprotein E in the Nervous System

V. Mouse models for AD A. The Tg2576 Mouse

VI. Summary

In the last chapter, we talked about human mental retardation syndromes—inherited deficiencies in learning and memory that manifest themselves from birth. In this chapter, we move to the other end of the developmental spectrum and will discuss aging-related memory dysfunction. In particular we will focus on Alzheimer's disease (AD) as an example of an inherited memory disorder that does not manifest itself until adulthood is reached. We will focus on inherited forms of AD not because they are the most prevalent but rather because they are the forms most tractable for experimental investigation at present. This is because inherited forms of AD, being gene-based, lend themselves to investigation using genetically engineered mice. As we have seen throughout the book, the recent advent of the capacity for genetic engineering in animal models holds the promise of a watershed of new insights into all aspects of memory, including investigating aging-related memory dysfunction such as AD.

In this chapter, I will present an overview of the clinical and pathological manifestations of AD. I will discuss in particular the emerging hypothesis that amyloid beta (Ap) is the proximal causative agent for AD. We also will discuss other important molecular events involved in AD

pathogenesis, always with an eye toward how these events might impinge upon the molecular mechanisms for learning and memory that we have been discussing in detail throughout the book. I also will spend a little time going over new mouse models that are relevant to AD, in keeping with our motif of investigating rodent models and behavioral paradigms of relevance to memory.

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Unraveling Alzheimers Disease

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