Alzheimer's Syndrome, Not Alzheimer's Disease
Not until 1993-94 did researchers agreed that AD had a heterogenous etiology that shared the same clinical (behavioral and cognitive) presenration, and recent research suggests that different pathogenic pathways lead to a similar pathologic endpoint.
Abstract
I n 1907, Alois Alzheimer presented a case of a 57-year-old female brought to him by her husband because of her paranoid thoughts.1 He noted the patient suffered from multiple cognitive deficits and, upon autopsy, the patient had intraneuronal formation of dense argentophilic fibrils, which are now referred to as neurofibrillatory tangles.i The next major step forward did not occur until 1984 when the National Institute of Neurological, Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) published the first standardization of clinical criteria for Alzheimer's Disease (AD).3 The clinical diagnosis of Alzheimer's disease rested upon excluding other causes of dementia. The diagnosis of AD, was classified as possible, probable, and definite. The definite diagnosis of AD required, in addition to the criteria for probable AD, the histopathological evidence of widespread senile plaques and neurofibrillatory tangles distributed throughout the cerebral cortex." Thus, the clinical diagnosis of AD rested upon a constellation of behavioral and cognitive symptoms. There are no biochemical markers for the disease. The next step in understanding the disease was the exploration of risk factors and different etiologies for the disease. Not until 1993-94 did researchers agreed that AD had a heterogenous etiology that shared the same clinical (behavioral and cognitive) presenration.v " Moreover, recent research suggests that different pathogenic pathways lead to a similar pathologic endpoint." In this regard, AD may be more of a syndrome than a disease. Evidence to support this theory can be witnessed by exploring the known risk factors for this condition such as advancing age, head trauma, and genetic predisposition.l The syndromal nature of the disease cannot be better exemplified than by exploring the genetic risk factors for the disease. There are three chromosomal abnormalities that cause Alzheimer's Disease."!"!" The three chromosomal abnormalities share the same clinical picture. Moreover, they share only a part of the pathogenesis yet result in the same final pathological picture.4,15-18 Recent studies have revealed that each chromosomal abnormality for the development of AD results in an accumulation of insoluble beta amyloid within cortical and subcortical neurons. IO,15,19-22 The pathogeneses that occurs before these depositions of amyloid, however, are differenr.r" Abnormal chromosome 21 can lead to an altered Amyloid Precursor Protein (APP).'2,'5,23 Six known mutations in the gene encoding APP are linked to the onset of AD.11-14The onset of this form of Alzheimer's Disease occurs between ages 50 and 60. 19