1 in 4 'Alzheimer's' patients don't have Alzheimer's

From Reza Hosseini Ghomi, MD, MSE on LinkedIn:

40% of people over 85 have a brain disease you've never heard of.

It's called LATE, and it's been hiding in plain sight for decades.

LATE: Limbic-predominant Age-related TDP-43 Encephalopathy

Until 2019, these patients were misdiagnosed as having Alzheimer's disease. The symptoms look identical. Memory loss, confusion, decline in daily functioning.

But the underlying brain pathology is completely different.

Here's what I've learned diagnosing hundreds of dementia cases.

LATE vs Alzheimer's — the critical differences:

Age of onset:

↳ LATE: Usually after 80

↳ Alzheimer's: Can start in 60s-70s

Progression:

↳ LATE: Slower, more gradual decline

↳ Alzheimer's: More predictable timeline

Brain changes:

↳ LATE: TDP-43 protein accumulation in limbic regions

↳ Alzheimer's: Amyloid plaques and tau tangles throughout cortex

Response to treatment:

↳ LATE: Doesn't respond to Alzheimer's medications

↳ Alzheimer's: May respond to cholinesterase inhibitors

Why this matters for families:

I've had patients taking Alzheimer's medications for years with no benefit. Their families assumed the drugs weren't working because the disease was "too advanced."

The real reason: They had LATE, not Alzheimer's.

LATE typically affects:

↳ Hippocampus and amygdala first (memory and emotion centers)

↳ Causes "hippocampal sclerosis" — shrinkage of memory structures

↳ Often coexists with Alzheimer's pathology (mixed dementia)

↳ More common in women and people with kidney disease

The diagnostic challenge:

Currently, LATE can only be definitively diagnosed at autopsy. But we're developing biomarkers to identify it in living patients.

New blood tests and advanced brain imaging may soon help us distinguish LATE from Alzheimer's during life.

This matters because:

↳ Different diseases need different treatment approaches

↳ LATE research is 10 years behind Alzheimer's research

↳ Families deserve accurate prognosis information

↳ Clinical trials need properly characterized patient populations

What I tell families in my clinic:

If your loved one has dementia that started after age 80 and isn't responding to Alzheimer's medications, LATE might be the explanation.

This doesn't change the care approach, but it can provide clarity about why certain treatments aren't working.

The future of LATE research:

↳ Specific biomarkers are in development

↳ Targeted therapies being investigated

↳ Better understanding of risk factors emerging

↳ Combination with Alzheimer's pathology being studied

Recognition of LATE has revolutionized how we think about dementia in the very elderly. It's not just "old Alzheimer's" — it's a distinct disease that needs its own research and treatment pathways.

💬 Comment if you've experienced unexplained treatment resistance in a family member with dementia

♻️ Repost if you think accurate dementia diagnosis matters

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