Early. Onset. |

OK. It’s bogeyman time.

Alzheimer’s! Yes. Even more than cancer- this word scares the bejesus out of us.

Once you have reached the age where a membership in AARP (the organization that wants you to forget it’s name was the American Association of Retired Persons) is possible (that means you have attained the ripe old age of 50 or higher), the fear of Alzheimer’s begins to pervade the little things we humans do Because we all perpetually forget some things.

Now, some of us clearly met the standard of the Absent-Minded Professor for decades. I’m certainly one of them. So, you can bet I leave my keys in a set spot all the time, so I never have to panic each morning- am I losing it?

And, I’ve just finished reading a book by one of my favorite authors (Philip Margolin, The 3^rd Victim), which addresses early onset Alzheimer’s in a most compassionate way. (His protagonist, the attorney Regina Barrister, confronts her growing memory lapses throughout the mystery novel.)

Given that so many folks have volunteered to have their DNA analyzed (without realizing that the police also notice this- and have used these databases to nab a few criminals off the street), finding out that a certain gene variant (in this case ApoE4) may prevail in their makeup. Have one variant indicates Alzheimer’s may be in the cards. Having two such variants pretty much assures one will develop at least late-onset dementia. We can also undergo a spinal tap or a PET scan (which runs up a tab of about $ 4K)- but then what would (or could) we do. That information has no effect on our prognosis.

The real problem is that we don’t know for sure what causes Alzheimer’s. Ok. Since 1993, we knew the presence of the variant of apolipoprotein E (hence the name ApoE4) multiplies our chances to manifest Alzheimer’s- at least by a factor of 4. (ApoE4 affords our brains the ability to develop plaques; those plaques kill brain neurons and disrupt our brain pathways.)

It’s also possible that ApoE4 effects an immune response from Tau proteins. Most folks with Alzheimer’s manifest both the amyloid plaques and intracellular Tau tangles. That finding was confirmed by Dr. David Holtzman (Washington University School of Medicine) and some 33 additional researchers, who published their data in Nature. They disabled the human ApoE gene variants (ApoE2, 3, and 4) in some mice (leaving others with their variants intact) and crossed them with “tau” mice; the results were profound. All mice that had an ApoE variant developed tau tangles and neurodegeneration. Those with only viable tau proteins manifested little neuronal death (or even none at all).

That’s not all this research team did. They took the immune cells (microglia and astrocytes) that express human ApoE4, mixed them with neurons that contained the tau protein, and cultured them. The resulting immune response managed to kill a slew of neurons.

This led the team to propose that Beta amyloid is an important trigger for Alzheimer’s, with tau deposits “finishing” up the trauma.

That still didn’t give us a clear path to treat Alzheimer’s, though.

We’ll continue this discussion tomorrow.