Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently recognized disease entity characterized by a stereotypical TDP-43 proteinopathy in older adults, often associated with amnestic dementia. LATE neuropathological change (LATE-NC) is distinguished from frontotemporal lobar degeneration with TDP-43 pathology by its epidemiology and restricted neuroanatomical distribution. LATE-NC is common, affecting up to 50% of individuals over 80 years old, and is associated with significant cognitive impairment. It often coexists with amyloid-β plaques and tauopathy. LATE shares pathogenetic mechanisms with both frontotemporal lobar degeneration and Alzheimer's disease but has disease-specific mechanisms. Genetic studies have identified five risk genes: GRN, TMEM106B, ABCC9, KCNMB2, and APOE. LATE has a growing public health impact, particularly in the 'oldest-old' population. A working group developed diagnostic criteria and staging guidelines for LATE-NC, proposing a three-stage system based on TDP-43 immunohistochemistry in three brain areas: amygdala, hippocampus, and middle frontal gyrus. LATE-NC is associated with hippocampal atrophy, frontal cortex atrophy, and other brain regions. MRI studies show that LATE-NC is associated with significant brain atrophy outside the medial temporal lobes. LATE-NC is often comorbid with ADNC and other pathologies. The clinical features of LATE include an amnestic dementia syndrome, with cognitive impairment greater than that attributed to ADNC alone. LATE-NC is associated with a distinct neurocognitive profile, with prominent episodic memory impairment. LATE-NC is associated with increased risk of neuropsychiatric symptoms such as agitation and aggression. Public health impact of LATE is significant, with LATE-NC affecting up to 20% of individuals over 80 years old. LATE-NC is a common neuropathological change in older adults, and its recognition is important for understanding dementia pathogenesis. Further research is needed to develop diagnostic tools and treatments for LATE.Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently recognized disease entity characterized by a stereotypical TDP-43 proteinopathy in older adults, often associated with amnestic dementia. LATE neuropathological change (LATE-NC) is distinguished from frontotemporal lobar degeneration with TDP-43 pathology by its epidemiology and restricted neuroanatomical distribution. LATE-NC is common, affecting up to 50% of individuals over 80 years old, and is associated with significant cognitive impairment. It often coexists with amyloid-β plaques and tauopathy. LATE shares pathogenetic mechanisms with both frontotemporal lobar degeneration and Alzheimer's disease but has disease-specific mechanisms. Genetic studies have identified five risk genes: GRN, TMEM106B, ABCC9, KCNMB2, and APOE. LATE has a growing public health impact, particularly in the 'oldest-old' population. A working group developed diagnostic criteria and staging guidelines for LATE-NC, proposing a three-stage system based on TDP-43 immunohistochemistry in three brain areas: amygdala, hippocampus, and middle frontal gyrus. LATE-NC is associated with hippocampal atrophy, frontal cortex atrophy, and other brain regions. MRI studies show that LATE-NC is associated with significant brain atrophy outside the medial temporal lobes. LATE-NC is often comorbid with ADNC and other pathologies. The clinical features of LATE include an amnestic dementia syndrome, with cognitive impairment greater than that attributed to ADNC alone. LATE-NC is associated with a distinct neurocognitive profile, with prominent episodic memory impairment. LATE-NC is associated with increased risk of neuropsychiatric symptoms such as agitation and aggression. Public health impact of LATE is significant, with LATE-NC affecting up to 20% of individuals over 80 years old. LATE-NC is a common neuropathological change in older adults, and its recognition is important for understanding dementia pathogenesis. Further research is needed to develop diagnostic tools and treatments for LATE.