In neurology, to understand neurodegeneration is the "holy grail". So far, there are only a couple of neurodegenerative diseases whose cause have been found. One is the Prion related diseases and the other is the familial ALS which is due to mutation in the SOD gene. In these cases the neurons undergo programmed cell death called, "Apoptosis". It is quite possible that apoptosis is the basis of all neurodegenerative neurological diseases, though i am not sure. The common thread among the neurodegenerative diseases is that we see accumulation of different kinds of proteins, such as beta-amyloid in Alzheimers, lewy bodies in parkinson's disease, pick bodies in the Pick's disease, ubiquitin, alpha-synuclein, hyper-phosphorylation of the tau protein, which is a component of the microtubules that run along the axons and along which the neuronal cell body (soma) transports various proteins to the synaptic endings and vice versa. There is very little to none inflammation present. Thanks.

Neurodegeneration covers a wide spectrum of neurological disorders. These disorders can manifest with many different symptoms, including cognitive impairment, speech difficulties, and motor dysfunction. The underlying pathological hallmark shared neurodegenerative

disorders is the loss of neuronal populations in the brain and/or spinal cord.

The particular areas of the brain and spinal cord in which neuronal loss occurs dictate the clinical features of a given neurodegenerative disorder. Neurodegenerative disorders include common and uncommon diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD),

myotrophic lateral sclerosis (ALS), Huntington’s disease (HD), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasaldegeneration (CBD), frontotemporal dementia (FTD), spinocerebellar ataxia (SCA) disorders,

and spinal muscular atrophy, among others.

Common pathological features shared among the neurodegenerative disorders are neuronal cell loss, gliosis, atrophy, and pathological protein inclusions.

In AD, the key pathological features include neuron loss, amyloid plaques, and neurofibrillary tangles. Atrophy is predominant in temporal and parietal cortex because of neuronal loss. Neuron loss is predominant in layers 3 and 5 of the neocortex, CA1 region of the hippocampus,

and layers 2 and 5 in the entorhinal cortex. Plaques are composed of abnormal neurites and glial processes surrounding a central core composed of β-amyloid. β-Amyloid can also be found in the cerebral blood vessels. Plaques are mostly found in cerebral cortex

and hippocampus.

Neurofibrillary tangles are composed of excessively phosphorylated tau

protein that form paired helical filaments that are deposited in soma and processes of neurons.

In the earliest stages, neurofibrillary tangles develop in the transentorhinal cortex and then spread to the entorhinal cortex and hippocampus prior to neocortical regions. These tangles are not specific to AD, but are found in other neurodegenerative disorders, including PSP and dementia pugilistica.

PD was classically described as caused by loss of dopaminergic neurons within the substantia nigra with associated Lewy bodies, cytoplasmic aggregates made up predominantly of alpha-synuclein .

ALS is marked by the loss of lower motor neurons in the anterior horn of the spinal cord and cranial motor nuclei. In addition, there is degeneration and loss of upper motor neurons in the motor cortex, particularly involving Betz cells. With the loss of these upper motor neurons, there is gliosis of the lateral corticospinal tracts. Affected muscles show grouped atrophy caused by denervation of muscle fibers. Ubiquitin-positive, proteinaceous inclusions are seen but are of variable composition compared to AD and PD, in which β-amyloid and tau or alpha-synuclein, respectively, are the predominant components. In certain familial forms of ALS, proteins that are the product of the related gene mutation can be found within the inclusions, including superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS), among others.

HD is marked by predominant atrophy of the striatum and cortex. The caudate is particularly affected with significant loss of medium spiny neurons and less loss of glial cells. Inclusions

found in the disorder are composed predominantly of the huntingtin protein and tend to be localized to the nucleus.