This index provides comprehensive information about brain regions implicated in neurodegenerative diseases. Understanding the vulnerability of specific brain regions is crucial for elucidating disease mechanisms, identifying biomarkers, and developing therapeutic interventions. Each brain region page includes information about its normal function, involvement in neurodegenerative diseases, neuroanatomy, connectivity, and relevant research findings. [1]
The brain is organized into functionally distinct regions, each with specific roles in cognition, movement, sensation, and autonomic control. Neurodegenerative diseases selectively target particular brain regions, producing characteristic clinical syndromes and neuropathological patterns. Understanding regional vulnerability provides insights into disease mechanisms and guides therapeutic development. [2]
The cerebral cortex is the outer layer of the brain responsible for higher cognitive functions. In Alzheimer's disease, cortical atrophy begins in the entorhinal cortex and hippocampus before spreading to other regions. The cortex shows characteristic amyloid plaques and neurofibrillary tangles in AD. Frontotemporal dementia shows selective frontal and/or temporal cortical atrophy. [3]
The limbic system is critical for memory and emotional processing. Many neurodegenerative diseases affect limbic structures early in their progression. [4]
The hippocampus is essential for memory formation and spatial navigation. It is one of the first regions affected in Alzheimer's disease, showing significant atrophy on MRI even in preclinical stages. Severe CA1 neuron loss occurs in AD. [5]
The amygdala processes emotions and is involved in emotional memory. It is affected early in AD and shows Lewy body pathology in DLB.
The entorhinal cortex serves as the major gateway between the hippocampus and neocortex. It is the first cortical region to show tau pathology in AD.
The basal ganglia are involved in motor control and habit learning. Degeneration of the substantia nigra pars compacta within the basal ganglia is the hallmark of Parkinson's disease. More than 70% loss of dopaminergic neurons occurs by clinical diagnosis.
The brainstem controls vital functions including breathing, heart rate, and sleep. Brainstem nuclei are affected early in various neurodegenerative diseases.
The substantia nigra is the primary site of dopaminergic neuron loss in Parkinson's disease. The pars compacta contains neuromelanin-pigmented neurons that are selectively vulnerable.
The locus coeruleus is the primary source of norepinephrine in the brain. It shows early tau pathology even in young adults.
The raphe nuclei are the source of serotonin. They are affected in PD and contribute to depression and sleep disorders.
The cerebellum coordinates movement and may contribute to cognitive function. While relatively spared in AD, it shows significant pathology in some forms of FTD and ataxias.
The thalamus relays sensory and motor information. It is involved in various neurodegenerative diseases and serves as a target for deep brain stimulation.
Berriman J. Regional brain vulnerability in neurodegenerative disease. Nat Rev Neurol. 2023. ↩︎
Seeley WW, Crawford R, Rascovsky K, et al. Frontal paralimbic network atrophy in neurodegenerative diseases. Arch Neurol. 2008. ↩︎
Braak H, Alafuzoff I, Arzberger T, et al. Staging of Alzheimer disease neurofibrillary pathology. Acta Neuropathol. 2006. ↩︎
Jack CR Jr, Knopman DS, Jagust WJ, et al. Hypothetical model of dynamic biomarkers of Alzheimer's disease. Lancet Neurol. 2010. ↩︎
Surmeier DJ, Obeso JA, Halliday GM. Selective neuronal vulnerability in Parkinson disease. Nat Rev Neurol. 2017. ↩︎