The Role of Pathology in Understanding Disease Processes

The pathological basis of disease refers to the structural and functional changes that occur within tissues and organs as a result of various disease processes. These changes can be visualized through histological stains, electron microscopy, immunohistochemistry, protein chemistry, molecular genetics, and biophysics. Pathologists play a crucial role in defining disease processes and mechanisms by observing structural alterations and conducting hypothesis-driven experimentation.

The study of pathology has delivered an understanding of disease that guides effective treatment and recognizes ineffective treatment, which has been particularly successful in providing insights for the treatment of acute diseases. However, in the setting of chronic diseases, where the relationship between basic pathology and pathophysiology is often misinterpreted, progress towards effective therapy has been slow. This is partly due to the pathologist's fascination with lesions, which can be visualized, such as senile plaques and neurofibrillary tangles in Alzheimer's disease.

In chronic diseases like Alzheimer's disease, the pathological changes develop over years, and it remains an open question whether such changes mark a movement toward health or death. Yet, studies addressing the pathogenesis of Alzheimer's disease are often dominated by the construct of a concrete lesion, which has led to a misconception of the relationship between pathology and chronic disease. To fulfill the ultimate goal of providing useful information that would guide treatment efforts, a more open-minded view of pathology by pathologists themselves is necessary.

The most direct test of the pathology hypothesis, vaccine therapy, has led to pathology reversal at the cost of increased morbidity and mortality with no cognitive benefits. This contradicted the prediction based on experimental models, where removal of amyloid-β (Aβ) or tau accumulation from genetically engineered animals effectively treats cognitive impairment.

Pathology's role in defining disease processes and protective responses has been crucial since its inception. It serves as the indispensable link between basic science and clinical disease, encompassing the defining of disease processes and mechanisms through observation of structural alterations, as well as hypothesis-driven experimentation. The careful study of pathology has delivered an understanding of disease sufficient to guide effective treatment and recognize ineffective treatment, which has been particularly successful in providing insights for the treatment of acute diseases.