Condition/Disorder	Key Pathological Finding(s)	Key Protein / Cellular Defect	Classic Macroscopic/Imaging Finding	Exam Hook / Clinical Vignette Clue
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."