Alzheimer Disease (Senile Dementia) Characterized by progressive memory loss, is increasingly common in developed countries as populations include more elderly persons Definitive diagnosis is made by microscopic examination of the brain at autopsy Histopathologic hallmark being an increased number of: –extracellular neuritic or senile plaques, which occur mostly in the cerebral cortex: collections of tortuous neuritic processes surrounding a central amyloid core Another important histologic feature is proliferation of intracytoplasmic neurofibrillary tangles: –bundles of filaments in the cytoplasm of neurons: major component is abnormally hyper- phosphorylated forms of the protein, tau Effects on neuronal function include: –altered region-to-region communication through mechanical effects on axons and dendrites –neuronal death, eliciting a local inflammatory response Bielschowsky stain, a modified silver stain

Astrocytomas Are CNS neoplasms derived from astrocytes It is the most common type of glioma (tumor of glial cells) and can occur in most parts of the brain or spinal cord It usually develops in the frontal and parietal lobes of the cerebrum and is most common in adults, especially middle-aged men At least three different types exist, the most malignant of which is glioblastoma multiforme: –This type usually grows quickly and spreads to other parts of the brain, so it is difficult to treat –tumor features: proliferation of cells with astrocytic properties vascular proliferation (arrows) as well necrosis is also typical of the glioma, but not demonstrated in the micrograph As for most brain tumors, the etiology is unknown

Multiple Sclerosis (MS) Chronic inflammatory disease of the CNS characterized by a loss of myelin –damaged patches called plaques (regions of demyelination) appear in seemingly random areas of the white matter Although its etiology remains enigmatic, a leading theory proposes an autoimmune or viral cause During periods of MS activity, leukocytes (T cells) are drawn to regions of white matter, which initiates an inflammatory response accompanied by loss of oligodendrocytes and axon demyelination Disease course is unpredictable, and the type and severity of symptoms can vary greatly No cure exists, but certain medications are used to treat symptoms

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease Most common form of neurodegeneration affecting the motor system Characterized by: –Muscle atrophy (“amyotrophic”) –Degneration of corticospinal tracts in lateral art of spinal cord (“lateral sclerosis”) Progressive neuromuscular disorder caused by destruction of specific neurons in the brain and spinal cord ALS belongs to a class of disorders known as motor neuron diseases and results in loss of nervous control of skeletal muscles, which leads to degeneration and atrophy of muscle fibers Respiratory muscles are ultimately affected; death is thus due to an inability to breathe ALS mostly affects men, although women also get the disorder, with the progression rate varying among individuals Its cause is uncertain, but several proposed hypotheses include glutamate toxicity, mitochondrial dysfunction, and autoimmune mechanisms Grossly, most evident changes are found in anterior roots of spinal cord, which are thin and gray (rather than white)