| Alzheimer's Disease (AD) | Extracellular Senile (Neuritic) Plaques; Intracellular Neurofibrillary Tangles (NFTs) | Beta-amyloid (Aβ) in plaques; Hyperphosphorylated Tau in tangles | Diffuse cortical atrophy; Ventricular enlargement (hydrocephalus ex vacuo); Hippocampal atrophy | "Gradual memory loss," "NFTs correlate with cognitive decline," "Low CSF Aβ42, High CSF Tau," "ApoE4 allele risk," "Basal nucleus of Meynert affected early." |
| Lewy Body Dementia (DLB) | Lewy Bodies (eosinophilic cytoplasmic inclusions) in cortex and brainstem | Alpha-synuclein | DAT scan shows reduced uptake in striatum. Mild generalized atrophy. | "Fluctuating cognition," "vivid visual hallucinations," "parkinsonism," "REM sleep behaviour disorder," "Severe neuroleptic sensitivity." |
| Frontotemporal Dementia (FTD) (Pick's Disease Subtype) | Pick Bodies (spherical, silver-staining inclusions); Pick/Balloon Cells (swollen neurons) | 3R Tau (a tauopathy) | Severe, focal "Knife-blade" atrophy of frontal and/or temporal lobes. | "Profound personality/behaviour change," "apathy or disinhibition," "language problems (aphasia)," "relative sparing of memory early on." |
| Huntington's Disease | Severe, selective loss of medium spiny neurons in the striatum. | Mutant Huntingtin protein (from CAG repeat expansion on Chr 4) | Marked atrophy of the caudate head; "Boxcar ventricles." | "CAG repeats," "triad of chorea, dementia, & psychiatric symptoms," "autosomal dominant inheritance." |
| Creutzfeldt-Jakob Disease (CJD) (Sporadic) | Spongiform encephalopathy (neuropil vacuolation), neuronal loss, astrogliosis. | Misfolded Prion Protein (PrPSc) with high beta-sheet content. | Rapidly progressive cerebral atrophy. DWI/FLAIR signal changes in cortex/basal ganglia. | "Rapidly progressive dementia + myoclonus," "14-3-3 protein in CSF," "triphasic sharp waves on EEG." |
| Variant CJD (vCJD) | Spongiform change + Florid Plaques (PrP core with vacuolar halo). | Misfolded Prion Protein (PrPSc) | "Pulvinar sign" on MRI (high signal in posterior thalamus). | "Young patient," "psychiatric symptoms first," "painful sensory symptoms," "positive tonsil biopsy." |
| HIV-Associated Dementia | Microglial nodules, perivascular macrophage infiltrates, Multinucleated Giant Cells (pathognomonic). | Indirect damage from HIV viral proteins (Tat, gp120) & inflammation. | Diffuse cerebral atrophy, most prominent in subcortical regions. | "IV drug user," "subcortical dementia (psychomotor slowing)," "weight loss," "Trojan horse" mechanism (entry via macrophages). |
| Schizophrenia | Reduced grey matter volume (hippocampus, thalamus). Subtle neuronal disorganization. | Neurodevelopmental; ? excessive synaptic pruning. | Enlarged lateral and third ventricles. Reduced planum temporale asymmetry. | Absence of gliosis (distinguishes it from neurodegenerative disorders). |
| Mood Disorders (Late-life Depression) | Non-specific small vessel ischemic changes. | N/A (vascular etiology) | White Matter Hyperintensities (WMH) on T2/FLAIR MRI. | "Late-onset depression," "vascular risk factors (hypertension, diabetes)," "poor treatment response." |
| Wernicke's Encephalopathy | Petechial hemorrhages, gliosis, neuronal loss in periventricular/periaqueductal grey matter. | Thiamine (B1) deficiency | High T2 signal or enhancement of mamillary bodies, thalamus, tectal plate. | "Alcohol misuse," "classic triad of confusion, ataxia, ophthalmoplegia." |
| Autism Spectrum Disorder (ASD) | Hypoplasia of cerebellar vermis; reduced Purkinje cell count. | Neurodevelopmental | Hypoplastic cerebellum on MRI. | "Stereotyped behaviours," "social communication deficits," "challenging behaviour." |
| Anti-NMDAR Encephalitis | Antibody-mediated receptor internalization and synaptic dysfunction. | Antibodies against NMDA receptor | Non-specific T2/FLAIR changes, often in medial temporal lobes. | "Young woman," "viral prodrome -> psychosis -> seizures & dyskinesias," "ovarian teratoma." |
| Anti-LGI1 Encephalitis | Antibody-mediated synaptic dysfunction. | Antibodies against LGI1 (VGKC-complex) | Medial temporal lobe T2/FLAIR hyperintensity. | "Subacute memory loss," "faciobrachial dystonic seizures (FBDS)," "hyponatremia (low sodium)." |
| Anti-CASPR2 Encephalitis | Antibody-mediated synaptic dysfunction. | Antibodies against CASPR2 (VGKC-complex) | Limbic encephalitis changes on MRI. | "Older man," "triad of limbic encephalitis, neuromyotonia (painful jerks/stiffness), and autonomic dysfunction." |
| Progressive Supranuclear Palsy (PSP) | Neurofibrillary tangles & coiled bodies in neurons and glia. | 4R Tau (a tauopathy) | Midbrain atrophy; the "Hummingbird Sign" on sagittal MRI. | "Early falls (especially backwards)," "vertical gaze palsy (downward first)," "axial rigidity," "poor levodopa response." |
| Multiple System Atrophy (MSA) | Glial Cytoplasmic Inclusions (GCIs) in oligodendrocytes. | Alpha-synuclein (a synucleinopathy) | "Hot Cross Bun" sign (MSA-C) or putaminal atrophy (MSA-P). | "Severe, early autonomic failure (orthostatic hypotension)," "+ parkinsonism OR cerebellar ataxia," "poor levodopa response." |
| Normal Pressure Hydrocephalus (NPH) | Impaired CSF absorption leading to ventricular distension. | N/A (CSF dynamics) | Ventriculomegaly out of proportion to cortical atrophy. | "Classic triad: Wacky, Wobbly, Wet" (Cognitive decline, Magnetic gait, Urinary incontinence). Potentially reversible. |
| Chronic Traumatic Encephalopathy (CTE) | Neurofibrillary Tangles (NFTs) clustered around small blood vessels at the depths of cortical sulci. | Hyperphosphorylated Tau | Generalized cerebral atrophy, cavum septum pellucidum. | "History of repetitive head trauma (e.g., boxing, football)," "Punch-Drunk Syndrome." |
| Multiple Sclerosis (MS) | Demyelinating plaques in CNS white matter. | T-cell mediated autoimmune attack on myelin. | Periventricular white matter lesions ("Dawson's fingers"). | Animal model: Experimental Autoimmune Encephalomyelitis (EAE). |
| Post-Traumatic Stress Disorder (PTSD) | N/A (functional/structural change, not classic pathology). | N/A | Reduced hippocampal volume (atrophy). Amygdala hyperactivity. | "Flashbacks, avoidance, hyperarousal," "history of trauma." |
| Traumatic Brain Injury (TBI) Prognosis | Axonal shearing, contusions. | N/A (physical injury) | N/A | "Duration of Post-Traumatic Amnesia (PTA) is the best predictor of long-term outcome." |